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High Sensitivity of the Human Circadian Melatonin Rhythm to Resetting by Short Wavelength Light
Abstract
The endogenous circadian oscillator in mammals, situated in the suprachiasmatic nuclei, receives environmental photic input from specialized subsets of photoreceptive retinal ganglion cells. The human circadian pacemaker is exquisitely sensitive to ocular light exposure, even in some people who are otherwise totally blind. The magnitude of the resetting response to white light depends on the timing, intensity, duration, number and pattern of exposures. We report here that the circadian resetting response in humans, as measured by the pineal melatonin rhythm, is also wavelength dependent. Exposure to 6.5 h of monochromatic light at 460 nm induces a two-fold greater circadian phase delay than 6.5 h of 555 nm monochromatic light of equal photon density. Similarly, 460 nm monochromatic light causes twice the amount of melatonin suppression compared to 555 nm monochromatic light, and is dependent on the duration of exposure in addition to wavelength. These studies demonstrate that the peak of sensitivity of the human circadian pacemaker to light is blue-shifted relative to the three-cone visual photopic system, the sensitivity of which peaks at approximately 555 nm. Thus photopic lux, the standard unit of illuminance, is inappropriate when quantifying the photic drive required to reset the human circadian pacemaker.
... Morning middle-wavelength light peaked at 525 nm can produce significantly greater phase advance compared to longer wavelengths (> 595 nm) (Wright et al., 2004). In subjects with dilated pupils, shortwavelength (λmax: 460 nm) suppress melatonin more significantly than middle-wavelength (green) light peaking at 555 nm during 6.5 h after midnight (Gooley et al., 2010;Lockley et al., 2003). Thapan et al., 2001(Thapan et al., 2001 proposed an action spectrum for narrowband lights with a peak at 424 nm to 548 nm, which can significantly suppress melatonin during 30 min of midnight in subjects with dilated pupils. ...
... In the studies investigating the effect of the time course, shortwavelength light (λmax: 460 nm) can sustain significant melatonin suppression in subjects with undilated pupils given a 2 h exposure during the late night, while 550 nm (λmax) light can significantly suppress melatonin only after 1 h exposure and cannot sustain its effect (Cajochen et al., 2005). Moreover, in subjects with dilated pupils, 6.5 h short-wavelength light (λmax: 460 nm) sustained its effect on melatonin suppression (Gooley et al., 2010;Lockley et al., 2003), in contrast, middle-wavelength light (λmax: 555 nm) had an approximately similar effect at a shorter duration (Lockley et al., 2003) (~90 min (Gooley et al., 2010). ...
... In the studies investigating the effect of the time course, shortwavelength light (λmax: 460 nm) can sustain significant melatonin suppression in subjects with undilated pupils given a 2 h exposure during the late night, while 550 nm (λmax) light can significantly suppress melatonin only after 1 h exposure and cannot sustain its effect (Cajochen et al., 2005). Moreover, in subjects with dilated pupils, 6.5 h short-wavelength light (λmax: 460 nm) sustained its effect on melatonin suppression (Gooley et al., 2010;Lockley et al., 2003), in contrast, middle-wavelength light (λmax: 555 nm) had an approximately similar effect at a shorter duration (Lockley et al., 2003) (~90 min (Gooley et al., 2010). ...
Light is detected in the eye by three classes of photoreceptors (rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs)) that are each optimized for a specific function and express a particular light-detecting photopigment.
The significant role of short-wavelength light and ipRGCs in improving alertness has been well-established; however, few reviews have been undertaken to assess the other wavelengths' effects regarding timing and intensity. This study aims to evaluate the impact of different narrowband light wavelengths on subjective and objective alertness among the 36 studies included in this systematic review, 17 of which were meta-analyzed.
Short-wavelength light (∼460–480 nm) significantly improves subjective alertness, cognitive function, and neurological brain activities at night, even for a sustained period (∼6h) (for λmax: 470/475 nm, 0.4 < |Hedges's g| < 0.6, p < 0.05), but except early morning, it almost does not show this effect during the day when melatonin level is lowest. Long-wavelength light (∼600–640 nm) has little effect at night, but significantly increases several measures of alertness at lower irradiance during the daytime (∼1h), particularly when there is homeostatic sleep drive (for λmax: ∼630 nm, 0.5 < |Hedges's g| < 0.8, p < 0.05). The results further suggest that melanopic illuminance may not always be sufficient to measure the alerting effect of light.
... Treatment strategies for circadian rhythm sleep disorders often involve behavioral interventions, such as light therapy and melatonin supplementation. Light is a powerful entraining agent for the circadian clock, with blue light being particularly effective in shifting circadian phase through its action on melanopsin-containing retinal ganglion cells (Lockley et al., 2003) [12] . However, chronic exposure to artificial light at night can lead to circadian misalignment, contributing to sleep disturbances and increased risks of metabolic and cardiovascular diseases (Walker et al., 2020) [24] . ...
... Treatment strategies for circadian rhythm sleep disorders often involve behavioral interventions, such as light therapy and melatonin supplementation. Light is a powerful entraining agent for the circadian clock, with blue light being particularly effective in shifting circadian phase through its action on melanopsin-containing retinal ganglion cells (Lockley et al., 2003) [12] . However, chronic exposure to artificial light at night can lead to circadian misalignment, contributing to sleep disturbances and increased risks of metabolic and cardiovascular diseases (Walker et al., 2020) [24] . ...
... o długości fali świetlnej 450-480 nm. Inspiracją do opracowania tej metody było odkrycie, że melanopsyna odpowiedzialna za zmianę rytmu okołodobowego jest najbardziej wrażliwa na takie światło [50]. Praktyka wykazała jednak, że zakres światła niebieskiego nie jest konieczny do skutecznej terapii światłem, a stosowanie samego światła niebieskiego nie jest efektywniejsze od BLT [51]. ...
... Znakomity efekt fototerapii depresji sezonowej przyczynił się do prowadzenia badań dotyczących wdrożenia takiego leczenia w innych rodzajach depresji. Ostatnie metaanalizy przynoszą istotne dowody na terapeutyczne działanie światła w depresji niesezonowej [50] oraz na potencjalizację poprzez fototerapię działania leków przeciwdepresyjnych [59]. Podjęto również próby stosowania terapii światłem w innych chorobach, zwykle jako wspomagania prowadzonego leczenia. ...
W bieżącym roku przypada czterdziesta rocznica publikacji artykułu, w którym po raz pierwszy użyto pojęcia choroby afektywnej sezonowej (Seasonal Affective Disorder - SAD). Obecnie SAD uznaje się jako szczególną kategorię choroby afektywnej. W klasyfikacji amerykańskiej Diagnostic and Statistical Manual of Mental Disorders. Fifth edition (DSM-5) sezonowość stanowi „wyznacznik” (specifier, with seasonal pattern) zarówno dla depresji nawracającej czyli tzw. dużego zaburzenia depresyjnego (ang. Major Depressive Disorder – MDD), jak i dla choroby afektywnej dwubiegunowej (CHAD) (ang. Bipolar Disorder). Najbardziej spektakularnym zjawiskiem z kręgu SAD jest depresja zimowa. Jej symptomatologia jest w dużym stopniu podobna do depresji atypowej, charakteryzującej się nadmiarem snu i głodem węglowodanowym. SAD może dotyczyć do 1/5 osób chorujących na depresję nawracającą lub CHAD i częściej występuje u kobiet. SAD można traktować jako ekstremalny przejaw zmian ośrodkowego układu nerwowego (OUN) związanych z okołorocznym rytmem oświetlenia. Różnice sezonowe funkcji OUN dotyczą m.in. sekrecji melatoniny, neuroprzekaźników dopaminy i serotoniny oraz osi podwzgórze-przysadka-nadnercza. W procesach okołodobowych (circadian) oraz około-rocznych (circannual) istotną rolę odgrywa czynność tzw. genów zegarowych (clock genes). SAD może stanowić spuściznę po człowieku neandertalskim. W depresji zimowej efekt leczniczy uzyskuje się za pomocą ekspozycji na jasne światło (bright light therapy – BLT), jak również na światło niebieskie (blue light) oraz za pomocą metody symulacji świtu (dawn simulation). Terapeutyczny efekt fototerapii stwierdzono również w depresji nie-sezonowej. Jako kontrapunkt tego mechanizmu, podjęto zachęcające próby leczenia stanów maniakalnych poprzez ograniczenie światła za pomocą okularów blokujących światło niebieskie (blue-blocking glasses).
... 14 Blue light-emitting waves are the most crucial component in the synchronisation of the circadian rhythm, especially when compared to green and yellow wavelengths. 6,15 A six-and-a-half-hour exposure to 460nm of blue light was shown to double the amount of time it takes to initiate the circadian phase when compared to 555nm of green light. 6,15 Natural blue light is also critical for increased cognition, alertness, and supressed melatonin secretion during the day. ...
... 6,15 A six-and-a-half-hour exposure to 460nm of blue light was shown to double the amount of time it takes to initiate the circadian phase when compared to 555nm of green light. 6,15 Natural blue light is also critical for increased cognition, alertness, and supressed melatonin secretion during the day. 6 Although blue light is important for FIGURE 1: The electromagnetic spectrum. ...
Blue light ranges from 400 to 490 nanometres on the visible portion of the electromagnetic spectrum and is emitted from common electronic devices such as televisions, smartphones, and computers. With current widespread access to and usage of such devices, concerns regarding exposure to blue light are being increasingly acknowledged. Blue light has been found to be damaging to the eyes and sleep patterns, due to a reduction in the body's natural production of the hormone melatonin. In response to this potential health problem, blue light blocking glasses have been developed, claiming to protect the eyes from strain and to aid sleep at night. Among current published literature, there is conflicting data as to the full extent of the efficacy of blue light blocking glasses. While some studies have found blue light blocking glasses to be effective, others have found no such effect. This paper reviews existing data on this health issue and the potential benefits of blue light eyewear.
... The circadian response's spectral sensitivity function is found to peak at 450-490 nm [19][20][21]. Recent discovery of intrinsically photosensitive retinal ganglion cells (ipRGCs) in human retina leads to various circadian quantifying metrics [22]. ...
... A solution has been presented for constructing a tunable luminaire with CCT values fixed for different day periods with varied intensity conditions. For 8.00 am to 12.00 pm, a spectrum with a blue peak at 455 nm is considered because it promotes awareness and increases activity levels [21]. A cooler tone with a CCT of 4872 K can be used for increased productivity. ...
This article deals with tracking a reference spectrum, enhancing the circadian entrainment of the occupants. The choice of the reference spectrum was made with an emphasis on maintaining the CCT, maintaining a CRI value of at least 80 for the general work area, and maintaining the luminous flux. Use of the Levenberg–Marquardt (LM) algorithm results in the optimal number of LEDs needed for spectrum synthesis. As a result, this work intends to offer a solution for making a luminaire. The percentage error in CCT for the simulated spectrums was less than 0.4%. The daylight spectrum is also selected as a reference spectrum so that close characteristics of sunlight are reached, meeting human comfort needs while also delivering the advantages of sunlight. This novel method of keeping a reference spectrum to design a LED luminaire for circadian entrainment with high luminous efficacy leads to the human-centric lighting system.
... Numerous investigations have demonstrated that a key element in the suppression of melatonin is the light's wavelength. In particular, because the short wavelength has been demonstrated to decrease melatonin (Lockley et al., 2013;Green et al., 2017), the human circadian pacemaker in the SCN is more sensitive to short or blue wavelength light (460 nm) than long or red wavelength light (555 nm). Although less so than light wavelength, light intensity has a detrimental impact on sleep (Knufinke et al., 2019). ...
Melatonin and pregabalin are two important compounds that are broadly used in the fields of physiological and medicinal sciences. Melatonin is a primary hormone mainly secreted by the pineal gland and plays an important role in regulating circadian rhythms, sleep-wake cycles, and neuroimmune processes. Its strong antioxidant anti-inflammatory and anti-apoptotic properties have protected it against a wide range of diseases, from cancer to neurological disorders. In this study, the synthesis of melatonin will be widely studied, mainly regarding its role in regulating circadian rhythms and sleep, and its possible therapeutic use in treating neurological diseases and inflammation-related disorders. Pregabalin is an analog of the neurotransmitter gamma-aminobutyric acid (GABA), with anticonvulsant, analgesic, and anxiolytic actions. Clinical practice has widely utilized it because studies indicate that it is useful in treating a variety of conditions: fibromyalgia, epilepsy, neuropathic pain, and generalized anxiety disorder. This article reviews aspects of the pharmacokinetics of pregabalin, its useful functions in pain treatment, and its impact on calcium channel regulation. The review also discusses indications of pregabalin in therapy, along with its possible side effects. This review article aims to consider the molecular processes underlying the activities of melatonin and pregabalin and their therapeutic potential for the management of sleep disorders, inflammation, and neurological diseases to future use of these compounds clinically.
... Conventional visual metrics for indoor lighting, such as photopic illuminance, are based on the photopic luminous efficiency function V(λ), which peaks in the green-yellow wavelength region at around 555 nm [15]. However, the spectral sensitivity for nonvisual effects peaks in the blue wavelength region (480-490 nm) [16]. This disparity implies that traditional photometry may not offer a reliable assessment for quantifying ipRGC-mediated circadian effects such as melatonin suppression. ...
The influence of light exposure on human circadian rhythms has been widely recognized. This effect is mediated by a phototransduction process projected by the intrinsically photosensitive retinal ganglion cells (ipRGCs). The process also involves signal inputs from visual photoreceptors. However, the relative contributions of each photoreceptor to this process remain unclear; accordingly, two different types of circadian lighting models have been proposed: (i) the melanopic illuminance model based solely on ipRGC activation, including melanopic equivalent daylight D65 illuminance (m-EDI) and equivalent melanopic illuminance (EML), and (ii) the circadian stimulus (CS) model, which considers the participation of both ipRGC and visual photoreceptors. However, the two models can yield conflicting predictions. In this study, we assessed and compared the accuracies of these circadian lighting models by fitting a substantial amount of experimental data extracted from multiple laboratory studies. Upon evaluating the results across all exposure durations, data-fitting accuracy of the intricate CS model did not surpass that of the much simpler melanopic illuminance model. Consequently, the latter appears to be the more suitable model for lighting applications. Moreover, a recurring limitation of prior research was revealed: the lighting spectra were not tailored to effectively reflect the fundamental distinctions between the two types of models. Therefore, drawing clear conclusions regarding the accuracies of the models is challenging. To address this problem, we introduced a method for designing contrast-spectra pairs. This method can provide lighting spectra to highlight the difference in circadian illuminance based on one model while keeping the circadian illuminance of others constant.
... The effective factor of light Studies that have been carried out reveal that there are three important factors affecting our response to light, namely wavelength, radiation duration, and light intensity. These factors control our cognitive functions and tasks [13,[55][56][57][58]. ...
Research conducted over the years has established that artificial light at night (ALAN), particularly short wavelengths in the blue region (~400–500 nm), can disrupt the circadian rhythm, cause sleep disturbances, and lead to metabolic dysregulation. With the increasing number of people spending considerable amounts of time at home or work staring at digital screens such as smartphones, tablets, and laptops, the negative impacts of blue light are becoming more apparent. While blue wavelengths during the day can enhance attention and reaction times, they are disruptive at night and are associated with a wide range of health problems such as poor sleep quality, mental health problems, and increased risk of some cancers. The growing global concern over the detrimental effects of ALAN on human health is supported by epidemiological and experimental studies, which suggest that exposure to ALAN is associated with disorders like type 2 diabetes, obesity, and increased risk of breast and prostate cancer. Moreover, several studies have reported a connection between ALAN, night-shift work, reduced cognitive performance, and a higher likelihood of human errors. The purpose of this paper is to review the biological impacts of blue light exposure on human cognitive functions and vision quality. Additionally, studies indicating a potential link between exposure to blue light from digital screens and increased risk of breast cancer are also reviewed. However, more research is needed to fully comprehend the relationship between blue light exposure and adverse health effects, such as the risk of breast cancer.
... Human response to light exposure is influenced by a multitude of factors, including the intensity and wavelength of light, duration of exposure, and individual physiological traits. Blue light, with wavelengths around 460-480 nanometers, is considered particularly effective in modulating human circadian rhythms [32]. The duration of light exposure also plays a critical role [33][34][35]. ...
Circadian rhythms, the natural cycles of physical, mental, and behavioral changes that follow a roughly 24-hour cycle, are known to have a profound effect on the human body. Light plays an important role in the regulation of circadian rhythm in human body. When light from the outside enters the eyes, cones, rods, and specialized retinal ganglion cells receive the light signal and transmit it to the suprachiasmatic nucleus of the hypothalamus. The central rhythm oscillator of the suprachiasmatic nucleus regulates the rhythm oscillator of tissues all over the body. Circadian rhythms, the natural cycles of physical, mental, and behavioral changes that follow a roughly 24-hour cycle, are known to have a profound effect on the human body. As the largest organ in the human body, skin plays an important role in the peripheral circadian rhythm regulation system. Like photoreceptor cells in the retina, melanocytes express opsins. Studies show that melanocytes in the skin are also sensitive to light, allowing the skin to “see” light even without the eyes. Upon receiving light signals, melanocytes in the skin release hormones that maintain homeostasis. This process is called “photoneuroendocrinology”, which supports the health effects of light exposure. However, inappropriate light exposure, such as prolonged work in dark environments or exposure to artificial light at night, can disrupt circadian rhythms. Such disruptions are linked to a variety of health issues, emphasizing the need for proper light management in daily life. Conversely, harnessing light’s beneficial effects through phototherapy is gaining attention as an adjunctive treatment modality. Despite these advancements, the field of circadian rhythm research still faces several unresolved issues and emerging challenges. One of the most exciting prospects is the use of the skin’s photosensitivity to treat diseases. This approach could revolutionize how we think about and manage various health conditions, leveraging the skin’s unique ability to respond to light for therapeutic purposes. As research continues to unravel the complexities of circadian rhythms and their impact on health, the potential for innovative treatments and improved wellbeing is immense.
... A prominent one is short-wavelength "blue" light from light-emitting diode (LED)s in devices like smartphones, tablet PCs, and laptops. The circadian system is highly responsive to short-wavelength light, and exposure to such light during nighttime has been observed to induce significant melatonin suppression and postpone the circadian rhythm (Cajochen et al. 2005;Figueiro and Overington 2016;Lockley et al. 2003;Wood et al. 2013). Also, Chang et al. (2015) observed that individuals who read an electronic book before bed compared to those who read a printed book took longer to fall asleep and reported decreased nocturnal sleepiness, along with suppressed melatonin levels. ...
Adolescent sleep disturbances and circadian delays pose significant challenges to mood and daytime functioning. In this narrative review, we explore the impact of light on sleep and highlight the importance of monitoring and managing light exposure in adolescents throughout the day and night. The benefits of daylight exposure in mitigating sleep and circadian disruptions are well-established; however, interventions targeting access to daylight in adolescents remain understudied and underutilized. The primary aim of this narrative review is to bring attention to this gap in the literature and propose the need for institutional-level interventions that promote access to daylight, especially considering adolescents' early school start times and substantial time spent indoors on weekdays. School-led interventions, such as active commuting to school and outdoor curriculums, have promising effects on sleep and circadian rhythms. Additionally, practical measures to optimize natural light in classrooms, including managing blinds and designing conducive environments, should also be considered. While future studies are necessary to facilitate the implementation of interventions, the potential for these school-level interventions to support adolescent sleep health is evident. Aiming for integration of individual-level regulation and institutional-level intervention of light exposure is necessary for optimal outcomes.
... Although the light emitted by most of LEDs appears to be white, LEDs have a peak emission in the blue color range (Tosini et al., 2016). In humans, circadian responses to light are most sensitive to blue light (Brainard et al., 2001;Thapan et al., 2001;Wright and Lack, 2001;Lockley et al., 2003). Men show a strong response to blue light in the late evening, even at very low levels, compared to women (Chellappa et al., 2017b). ...
Night shift workers have been associated with circadian dysregulation and metabolic disorders, which are tightly coevolved with gut microbiota. The chronic impacts of light-emitting diode (LED) lighting at night on gut microbiota and serum lipids were investigated. Male C57BL/6 mice were exposed to blue or white LED lighting at Zeitgeber time 13.5-14 (ZT; ZT0 is the onset of “lights on” and ZT12 is the “lights off” onset under 12-hour light, 12-hour dark schedule). After 33 weeks, only the high irradiance (7.2 J/cm²) of blue LED light reduced the alpha diversity of gut microbiota. The high irradiance of white LED light and the low irradiance (3.6 J/cm²) of both lights did not change microbial alpha diversity. However, the low irradiance, but not the high one, of both blue and white LED illuminations significantly increased serum total cholesterol (TCHO), but not triglyceride (TG). There was no significant difference of microbial abundance between two lights. The ratio of beneficial to harmful bacteria decreased at a low irradiance but increased at a high irradiance of blue light. Notably, this ratio was negatively correlated with serum TCHO but positively correlated with bile acid biosynthesis pathway. Therefore, chronic blue LED lighting at a high irradiance may harvest gut dysbiosis in association with decreased alpha diversity and the ratio of beneficial to harmful bacteria to specifically dysregulates TCHO metabolism in mice. Night shift workers are recommended to be avoid of blue LED lighting for a long and lasting time.
... In another study conducted in humans, it was reported that MLT secretion was suppressed by exposure to short-wavelength light (446-477 nm) (Brainard et al. 2001). It has been shown that light in the shortwavelength spectrum (465-485 nm) suppresses MLT production in mammals (Lockley et al. 2003;Mainster, 2006;Brainard et al. 2008). On the other hand, it is known that the effects of light on MLT synthesis and release are not similar among different species. ...
In this study, it was aimed to investigate the effects of red lighting on blood and milk melatonin levels, and milk quality. The experiment was carried out on 6 lactating Holstein Dairy cows, which were being reared at the Hümeyra Özgen Research and Application Farm, affiliated to Selcuk University Faculty of Veterinary Medicine. After a control period of 15 days in which night lighting was not applied (control group), night lighting was provided by LED bulbs emitting red light with a wavelength of 652 nm during the following 15-day trial period (experimental group). On days 5th, 10th and 15th days of the control and experimental groups, milk and blood samples were taken at the 06:00 am and at 06:00 pm.Serum and milk melatonin concentrations in the morning of the control, on days 5th, 10th and 15th; were 8.64±1.4, 7.02±0.97, 8.71±2.3, and 5.01±0.92, 5.23±0.35 , 3.93±0.81pg/ml, respectively while control evening group were respectively 8.59±1.8,7.53±2.14,8.35±0.94, 6.91±1.73, 6.8±1.27. It was obtained as 3.67±0.97 pg/ml. Serum and milk melatonin levels in the trial morning group were 10.93±2.06, respectively, on the same days; 15.37±2.6; 11.25±1.71 and 2.97±0.64; 5.7±1.06; While it was measured as 3.33±0.73 pg/ml, it was 14.83±3.11 in the trial evening group; 14.5±3.57; 12.95±4.09 and 4.42±0.61; 2.51±0.56; It was obtained as 2.48±0.79 pg/ml.It was observed that serum and milk melatonin levels and milk parameters were not adversely affected in the use of red LED lamps (652 nm) at night for 12h.
... Importantly, there is a threshold photic intensity required to obtain any effect, and a point of saturation at which higher intensities will not yield a greater magnitude response [32,[34][35][36][37]. Human studies under highly controlled conditions demonstrate a dose-response to white fluorescent light, with a half-saturation of ~90-125 lux and a range of responsiveness across ~2.5 orders of magnitude for melatonin suppression, phase-shifting, and alerting effects of light [36,38]. The dose-response function will shift depending on spectrum, and at a given intensity (that is not below threshold or above saturation), short-wavelength light is the most potent across various non-visual physiological functions and may have a longer lasting impact as well [33,39], with the greatest sensitivity to ~480 nm light as compared to all other tested wavelengths [32,34,[40][41][42][43][44][45]. Yet, architectural lighting typically tends toward moderate intensities, warmer color temperatures, and less short-wavelength emissions, which is not best for circadian health and safety in workplace settings [46]. ...
Shiftwork leads to myriad negative health and safety outcomes. Lighting countermeasures can benefit shiftworkers via physiological effects of light (e.g. alerting, circadian adjustment), and short-wavelength light is the most potent for eliciting those responses; however, limited work indicates it may not be required for alerting. We developed similar-appearing light boxes (correlated color temperature: 3000–3375 K; photopic illuminance: 260–296 lux), enriched (SW+, melanopic EDI: 294 lux) or attenuated (SW-, melanopic EDI: 103 lux) in short-wavelength energy, and implemented them on a high-security watchfloor. Efficacy and feasibility of these two novel lighting interventions were assessed in personnel working 12-hour night shifts (n = 47) in this within-participants, crossover study. For each intervention condition, light boxes were arranged across the front of the watchfloor and illuminated the entire shift; blue-blocking glasses were worn post-shift and before sleep; and sleep masks were used while sleeping. Comparisons between baseline and intervention conditions included alertness, sleep, mood, quality of life (QOL), and implementation measures. On-shift alertness (Karolinska Sleepiness Scale) increased in SW− compared to baseline, while changes in SW+ were more limited. Under SW+, both mood and sleep improved. Psychomotor vigilance task performance did not vary by condition; however, perceived performance and QOL were higher, and reported caffeine consumption and sleep onset latency were lower, under SW−. For both interventions, satisfaction and comfort were high, and fewer symptoms and negative feelings were reported. The addition of spectrally engineered lights to this unique work environment improved sleep, alertness, and mood without compromising visual comfort and satisfaction. This paper is part of the Sleep and Circadian Rhythms: Management of Fatigue in Occupational Settings Collection.
... As suggested by previous studies including our past work, the rationale for the improvement observed in dim light controls includes diminished exposure or darkness effects (with light visor caps), social cue and daily routine, response shift, and placebo effects [26,30,32]. Dim-red light is often used as the control to overcome placebo effects in studies involving bright light therapy [29,47] as intrinsically photosensitive retinal ganglion cells (ipRGCs) were thought to be insensitive to long wavelength (red) light [48,49]. Although it is yet to be proven, it is plausible that exposure to dim red light produces therapeutic effects. ...
Purpose
Bright light therapy holds promise for reducing common symptoms, e.g., fatigue, experienced by individuals with cancer. This study aimed to examine the effects of a chronotype-tailored bright light intervention on sleep disturbance, fatigue, depressive mood, cognitive dysfunction, and quality of life among post-treatment breast cancer survivors.
Methods
In this two-group randomized controlled trial (NCT03304587), participants were randomized to receive 30-min daily bright blue-green light (12,000 lx) or dim red light (5 lx) either between 19:00 and 20:00 h or within 30 min of waking in the morning. Self-reported outcomes and in-lab overnight polysomnography sleep study were assessed before (pre-test) and after the 14-day light intervention (post-test).
Results
The sample included 30 women 1–3 years post-completion of chemotherapy and/or radiation for stage I to III breast cancer (mean age = 52.5 ± 8.4 years). There were no significant between-group differences in any of the symptoms or quality of life (all p > 0.05). However, within each group, self-reported sleep disturbance, fatigue, depressive mood, cognitive dysfunction, and quality of life-related functioning showed significant improvements over time (all p < 0.05); the extent of improvement for fatigue and depressive mood was clinically relevant. Polysomnography sleep findings showed that a number of awakenings significantly decreased (p = 0.011) among participants who received bright light, while stage 2 sleep significantly increased (p = 0.015) among participants who received dim-red light.
Conclusion
The findings support using light therapy to manage post-treatment symptoms in breast cancer survivors. The unexpected symptom improvements among dim-red light controls remain unexplained and require further investigation.
Trial registration
ClinicalTrials.gov Identifier: NCT03304587, October 19, 2017.
... Contribution of OPN4 to mammalian circadian rhythms. Exposure to monochromatic blue light (460 nm) can suppress human melatonin levels and interfere with resetting circadian rhythm 106,107 . As part of this regulation, the photosensitive signal of OPN4 is first transmitted to the SCN through the retinohypothalamic tract (RHT), followed by the paraventricular nucleus and the intermediolateral nucleus via the polysynaptic circuit distributed in the SCN region, and finally to the release of melatonin innervated by the sympathetic nerve in the superior cervical ganglion (SCG) 108,109 . ...
Melanopsin (OPN4) is a light-sensitive protein that plays a vital role in the regulation of circadian rhythms and other nonvisual functions. Current research on OPN4 has focused on mammals; more evidence is needed from non-mammalian vertebrates to fully assess the significance of the non-visual photosensitization of OPN4 for circadian rhythm regulation. There are species differences in the regulatory mechanisms of OPN4 for vertebrate circadian rhythms, which may be due to the differences in the cutting variants, tissue localization, and photosensitive activation pathway of OPN4. We here summarize the distribution of OPN4 in mammals, birds, and teleost fish, and the classical excitation mode for the non-visual photosensitive function of OPN4 in mammals is discussed. In addition, the role of OPN4-expressing cells in regulating circadian rhythm in different vertebrates is highlighted, and the potential rhythmic regulatory effects of various neuropeptides or neurotransmitters expressed in mammalian OPN4-expressing ganglion cells are summarized among them.
... In modern society, light wields a profound influence on human physiology and psychology, making it a pivotal environmental factor for enhancing health and well-being [1][2][3][4][5]. As the majority of individuals now predominantly remain indoors, the need arises to meticulously craft lighting environments tailored to specific indoor spaces [6]. ...
The quality of indoor lighting significantly influences human well-being, emphasizing the need to integrate lighting planning into the architectural design process. To optimize indoor lighting conditions, light environment simulations are commonly employed. While much of the relevant literature clearly shows that simulations are widely used to predict lighting environments, there is limited active research validating these simulations. Therefore, this study aimed to assess the alignment between actual measurements and simulations, specifically focusing on daylight-induced glare. To achieve this, a comparative analysis and verification of glare levels between simulations and actual measurements were conducted that accounted for glare location and direction. Disparities between the simulated and measured glare levels were revealed contingent on the glare location and direction. These variations primarily arose from the simulation’s utilization of a fisheye field of view (FOV) for glare measurement. To improve the accuracy of glare analysis in simulations, it is advisable to follow the standards related to the human perception of glare, such as the human field of view (FOV), instead of solely depending on a fisheye FOV. The study’s limitations include challenges in environmental replication, minor measurement errors, and tree branch shading interference. Despite the potential for simulations to not replicate temporary glare effects, consistent differences with actual measurements indicate that the fisheye FOV was a key contributing factor.
... The magnitude of light-induced melatonin suppression is often examined to determine the effects of nighttime light on circadian rhythms [28][29][30][31]. Although melatonin suppression is closely linked to circadian phase resetting [32], the proposed functional separation between the two [33] necessitates a separate evaluation for a thorough understanding of the non-image-forming effect of light in humans. Our proposed method, which can estimate the 17 The horizontal axis shows the mean values of the estimated and measured DLMOs, and the vertical axis shows the difference between the estimated and measured DLMOs. ...
We aimed to establish a method for estimating dim light melatonin onset (DLMO) using mathematical slopes calculated from melatonin concentrations at three sampling points before and after sleep in children. The saliva of 30 children (mean age ± SD: 10.2 ± 1.3 years old) was collected under dim-light conditions up to six times every hour starting at 17:30 (t17), namely, 18:30 (t18), 19:30 (t19), 20:30 (t20), 21:30 (t21), 22:30 (t22), and 23:30 (t23), in the evening, and at 6:00 (t30) the following morning. We calculated SLOPEon (mathematical slope between melatonin concentrations at t18 and t20, t21 or t22), SLOPEoff (the slope between t20, t21 or t22, and t30), and ΔSLOPE, which is generated by subtracting SLOPEon
from SLOPEoff. DLMO was estimated by multiple regression analysis with the leave-one-out cross-validation (LOOCV) method using SLOPEon and SLOPEoff, and ΔSLOPE. The intraclass correlation coefficient (ICC) between the estimated and measured DLMOs was used as the index of estimation accuracy. DLMOs estimated using multiple regression equations with SLOPEon and SLOPEoff yielded significant ICCs for the measured DLMOs, with the largest ICC at t20 (ICC = 0.634). Additionally, the ICC between the estimated and measured DLMOs using the equation with ΔSLOPE was significant, with a larger ICC at t20 (ICC = 0.726) than that of the equation with SLOPEon and SLOPEoff. Our results showed that DLMO could be estimated with a certain level of accuracy from salivary melatonin levels at three time points before and after sleep in children.
... The preceding hormones have been reported to be light-responsive, which is the basis for the application of light therapy in regulating circadian and emotional disorders. For melatonin, it is widely reported that light suppresses melatonin, varies its secretion rhythmicity in phase and amplitude, and does so in a dose-dependent manner [10,120]. For 5-HT, the current consensus is that of light induction. ...
Aim
To provide an overview of the evidence on the effect of light therapy on sleep disturbance and depression, identify the light-active neural and hormonal correlates of the effect of light therapy on sleep disturbance comorbid depression (SDCD), and construct the mechanism by which light therapy alleviates SDCD.
Methods
Articles published between 1981 and 2021 in English were accessed using Science Direct, Elsevier, and Google Scholar following a three-step searching process via evolved keywords. The evidence level, reliability, and credibility of the literature were evaluated using the evidence pyramid method, which considers the article type, impact factor, and journal citation report (JCR) partition.
Results
A total of 372 articles were collected, of which 129 articles fit the inclusion criteria and 44% were at the top of the evidence pyramid hierarchy; 50% were in the first quarter of the JCR partitions. 114 articles provided specific neural and hormonal evidence of light therapy and were further divided into three groups: 37% were related to circadian regulation circuits, 27% were related to emotional regulation circuits, and 36% were related to hormones.
Conclusions
First, neural and hormonal light-active pathways for alleviating sleep disturbance or depression were identified, based on which the neural correlates of SDCD were located. Second, the light responses and interactions of hormones were reviewed and summarized, which also provided a way to alleviate SDCD. Finally, the light-active LHb and SCN exert extensive regulation impacts on the circadian and emotional circuits and hormones, forming a dual-core system for alleviating SDCD.
... Udowodniono, że intensywność światła w pomieszczeniach, w których spędza się dużo czasu, może zaburzać rytm dobowy i naturalne wydzielanie melatoniny [23,24]. Spowodowane jest to przede wszystkim działaniem światła niebieskiego, które ma udowodniony wpływ na zaburzenia rytmu dobowego [25][26][27]. Dużo światła niebieskiego znajduje się w polichromatycznym świetle, które nazywane jest światłem o wysokiej skorelowanej temperaturze barwowej (ang. correlated color temperaturę, CCT). ...
... SL presented next, emphasizing the importance of long exposures an d prior light adaptation, and making a case for a spectral ratio approach to lighting and design standards, using melanopic DER. He showed evidence as far back as 2003 (Lockley et al., 2003), confirmed in 2010 (Gooley et al., 2010) and in more recent unpublished work, that the cone component of responses diminishes with duration for human melatonin suppression, and circadian phase resetting. If a model were needed for shorter durations, then either a twochannel melanopic-photopic model or a three-channel model adding in S-cone responses would possibly serve better. ...
https://cie.co.at/publications/second-international-workshop-circadian-and-neurophysiological-photoreception
This Technical Note reports on the proceedings and consensus of the invited experts of The Second International Workshop on Circadian and Neurophysiological Photometry, 2019, Manchester (UK). This workshop acted on the basis of a consensus of the participants, who are also the advisers to this report, and led to the first international expert consensus recommendations on light exposure for health.
... Memelilerdeki merkezi sirkadiyen saat görevini yapan SCN nöronları, özellikle 380-500 nm uzunluğundaki mavi ışık fotonlarını, retinada bulunan foto-reseptörler ve ışığa duyarlı gangliyon hücreleri tarafından algılar. SCN, nihayetinde retino hipotalamik sistem aracılığıyla aktive olur ve bir takım genleri ve proteinleri de aktive eder (5 Sirkadiyen saat, memelilerde, hücre çoğalmasından, hücre ölümüne, DNA hasarının tamirinden, detoksifikasyon gibi metabolizma faaliyetlerine, büyüme faktörleri, pıhtılaşma faktörleri, immun fonksiyonlar ve birçok genin ekspresyonunu düzenleme, kalp atımı, beynin faaliyeti, böbrek aktivitesi (plazma akışı, idrar üretimi, kan basıncı, elektrolit ve su homeostazisi), endokrin sistem (kan şekerinin düzenlenmesi) (7), immun sistem (8) ve vücut ısısı (9) gibi fizyolojik olaylarda dahil olmak üzere biyolojik, genetik ve biyokimyasal olarak hemen hemen bütün hücresel olayları bir senkronizasyon dahilinde kontrol eder (10). ...
ÖZET Bedenimizde, yaklaşık 24 saatlik, otonom bir mekanizma tarafından düzenlenen, zamana bağlı döngüsel çalışan bir sistem vardır ve bu sistem sirkadiyen saat ya da sirkadiyen ritim olarak adlandırılır. Bu ritim uyku-uyanıklık, vücut ısısı, hormonların salgılanması, lokomotor aktivite ve iştah gibi çeşitli fizyolojik işlevlerin günlük rutinler halinde devam etmesini sağlar. Diğer taraftan, yapılan son çalışmalar yenilen yemeğin kalitesinin, içeriğinin (protein, karbonhidrat ya da yağ ağırlıklı olabileceği gibi, vitamin, mineral ve gıda katkı maddeleri gibi), zamanlamasının (öğün aralıkları, aydınlık ve karanlık süreçlerde yemek yeme), günlük yaşamımızdaki egzersiz ve uyku kalitesinin sirkadiyen metabolizmayı belirgin şekilde değiştirdiğini rapor etmiştir. Bireyin beslenme alışkanlıkları, enerji metabolizması, sirkadiyen saat, bedenin ritmi bir arada değerlendirildiğinde ortaya karışık bir metabolik yolak ağı çıkıyor. Bu yüzden, bu derlemede yaşam stili ve özellikle diyet kompozisyonu, uyku ve egzersiz açısından bakıldığında, sirkadiyen saatin ve bedenin ritminin, moleküler hücresel süreçleri ile genetik ve epigenetik temelinin aydınlatılması amaçlanmıştır.
... It starts to rise before two hours of bedtime (21), while the peak of melatonin secretion happens at midnight (69). Researchers found that the monochromatic blue light with a wavelength around 460 nm could better suppress melatonin production than any other wavelength (3,19,57,58,70,72,73,(78)(79)(80) ...
The effects of light on the human body can be generally classified into visual effects (IF) and non-visual effects (NIF). The IF is responsible for vision, while the NIF is responsible for many physiological, psychological, and behavioral rhythms. Daylight has been usually preferred over artificial light to meet the IF and NIF needs. The variable amount, spectral composition, timing, and duration of daylight throughout the day make it more potent in regulating circadian rhythms. Researchers reported that children and adolescents are more sensitive to lighting (both daylight and artificial light) than adults. This calls for special consideration for classrooms design as children spend around 30% of their life in school. Decisions made at the early stages of classroom design significantly impact the visual and non-visual benefits obtained from light, as the built environment can alter the light characteristics inside spaces. These decisions also influence the energy performance of classrooms and schools. This study uses multi-objective optimization to find the optimal classroom design in different climate zones in the U.S. based on visual, non-visual, and energy performance criteria. The visual benefits of daylight are expressed as the daylighting conditions at the horizontal desk-plane, while the non-visual benefits are expressed as the daylighting conditions at the vertical eye-level.
Two classrooms-corridors typologies are explored in this dissertation: classrooms connected to single-loaded corridors and classrooms connected to double-loaded corridors. The optimal classrooms design and the design parameters’ level of importance have been identified for both typologies. The Department of Energy (DOE) primary school reference building has been used as a reference model as it represents 70% of U.S. schools. Results have shown that there are similar optimal solutions in terms of each objective across closely located climate zones for the single-loaded corridor typology. The daylighting and energy performance of these classrooms is mainly influenced by the window orientation and window to wall ratio (WWR). The classroom design with the best overall performance in all objectives has
rectangular plan and a northeast oriented window. All optimal solutions have 3-5% higher window-to-wall ratio (WWR), higher window head height, and 25-35% less energy use than the reference classroom.
Finding the optimal design of classrooms connected to double-loaded corridors is more complex. The oppositely oriented classrooms have competing objectives to improve their daylighting performance. The results indicate that the 3:2 width-to-depth plan shape in most optimal solutions performs better than the 5:4 width-to-depth plan of the reference model. Accordingly, wider windows and higher head height in the optimal design were able to allow more daylighting to the depth of the oppositely oriented classrooms while reducing the energy use. The results show that optimal classrooms’ design connected to double-loaded corridors, including window dimensions, orientation, and WWR vary by the climate zone. Although WWR is the most important design parameter on horizontal desk-plane and vertical eye-level for most cases, other parameters can be at least equally important especially for the vertical eye-level daylighting across different climate zones. The results of this dissertation can give guidance to architects, designers, and decision makers on classrooms design across studied climate zones.
... Red light caught our attention because light regulates the sleepawake cycle via the intrinsically photosensitive retinal ganglion cells (ipRGCs), and the melanopsin cells expressed in ipRGCs are the least sensitive to red light, which might disrupt the original sleep-awake rhythm of the organism less than white light does (6,7). Red light is often used as a light source for nighttime illumination in laboratories, and some scholars believe that artificial red light can reduce sleepawake cycle disruption at night and improve sleep more than ordinary white light (8)(9)(10). ...
Introduction
This study aimed to determine the influence of red light on objective sleep and the relationship between mood and sleep among individuals with insomnia disorder (ID).
Method
57 individuals with insomnia symptoms and 57 healthy participants were randomly divided into three groups (red- and white-light groups, and the black control group), which received different light treatments for 1 h before bedtime. The emotions and subjective alertness of participants were evaluated using Positive and Negative Affect Schedule scales (PANAS) and Karolinska Sleepiness Scale (KSS), their sleeping data were recorded using polysomnography (PSG).
Result
The negative emotion scores were higher in the healthy subject-red light (HS-RL) group than in the HS-white light (WL) and HS-black control (BC) groups (p < 0.001). The anxiety and negative emotion scores were higher in the ID-RL group than in the ID-WL and ID-BC groups (p = 0.007 and p < 0.001, respectively). The KSS scores were lower in the RL group than in the WL and BC groups for both HS and ID group (both p < 0.001). The SOL was shorter in the HS-RL group than in HS-WL group (p = 0.019). Compared with the HS-BC group, the HS-RL group had an increase in microarousal index (MAI) and N1% (p = 0.034 and p = 0.021, respectively), while the total sleep time (TST) and sleep efficiency (SE) decreased (p = 0.001 and p < 0.001, respectively). Compared with the ID-WL group, the SOL was shorter in the ID-RL group (p = 0.043), while TST, SE, number of microarousals (NMA), and numbers of cycles of REM period were increased (p = 0.016, p = 0.046, p = 0.001, and p = 0.041, respectively). Compared with the ID-BC group, the ID-RL group had increases in the SOL, WASO, and the numbers of cycles and NMA in REM period (p = 0.038, p = 0.005, p = 0.045, and p = 0.033, respectively), and a decrease in SE (p = 0.014). The effects of ID-WL (vs. ID-RL group) and ID-BC (vs. ID-RL group) on SOL were mediated by negative emotions (mediating effects were − 37.626 and − 33.768, respectively).
Conclusion
Red light can increase subjective alertness, anxiety, and negative emotions in both healthy subjects and people with ID, which can affect sleep directly or indirectly via the mediating effect of negative emotions.
... Rationale for the improvement observed in dim light controls includes diminished exposure or darkness effects (with light visor caps), social cue and daily routine, response shift, and placebo effects [23,27,29]. Dim-red light is often used as the control to overcome placebo effects in studies involving bright light therapy [26,41] as intrinsically photosensitive retinal ganglion cells (ipRGCs) was thought to be insensitive to long wavelength (red) light [42,43]. Although it is yet to be proven, it is plausible that exposure to dim red light produces therapeutic effects. ...
Purpose
Bright light therapy holds promise for reducing common symptoms, e.g., fatigue, experienced by individuals with cancer. This study aimed to examine the effects of a chronotype-tailored bright light intervention on sleep disturbance, fatigue, depressive mood, cognitive dysfunction, and quality of life among post-treatment breast cancer survivors.
Methods
In this two-group randomized controlled trial (NCT03304587), participants were randomized to receive 30-min daily bright blue-green light (12,000 lux) or dim red light (5 lux) either between 19:00–20:00 h or within 30 min of waking in the morning. Self-reported outcomes and in-lab overnight polysomnography sleep study were assessed before (pre-test) and after the 14-day light intervention (post-test).
Results
The sample included 30 women 1–3 years post-completion of chemotherapy and/or radiation for stage I to III breast cancer (mean age = 52.5 ± 8.4 years). There were no significant between-group differences in any of the symptoms or quality of life (all p > 0.05). However, within each group, self-reported sleep disturbance, fatigue, and depressive mood, and quality of life-related functioning showed significant improvements over time (all p < 0.01); the extent of improvement for fatigue and depressive mood was clinically relevant. Polysomnography sleep findings showed that number of awakenings significantly decreased (p = 0.011) among participants received bright light, while stage 2 sleep significantly increased (p = 0.015) among participants received dim-red light.
Conclusion
The findings provide some evidence to support using chronotype-tailored light therapy to manage sleep disturbance, fatigue, depressive mood in post-treatment breast cancer survivors. The unexpected symptom improvements among dim-red light controls remain unexplained and requires further investigation.
ClinicalTrials.gov Identifier:
NCT03304587 Study was registered on October 19, 2017.
... Shift work was found to disrupt the circadian rhythm; therefore, preventative or risk-reducing therapies are required. The role of melatonin and light exposure in circadian disruption was examined in additional cited articles in this cluster [96][97][98][99]. Human melatonin production is suppressed by bright lighting, particularly by shorter light wavelengths, such as those under 525 nm [97]. ...
Prostate cancer is the most commonly diagnosed cancer in the United Kingdom. While androgen-deprivation therapy is the most common treatment for prostate cancer, patients undergoing this treatment typically experience side effects in terms of sleep disturbances. However, the relation between prostate cancer and sleep and the way in which sleep interventions may benefit oncological patients is underinvestigated in the literature. The current study aims to review in a data-driven approach the existing literature on the field of prostate cancer and sleep to identify impactful documents and major thematic domains. To do so, a sample of 1547 documents was downloaded from Scopus, and a document co-citation analysis was conducted on CiteSpace software. In the literature, 12 main research domains were identified as well as 26 impactful documents. Research domains were examined regarding the link between prostate cancer and sleep, by taking into account variations in hormonal levels. A major gap in the literature was identified in the lack of use of objective assessment of sleep quality in patients with prostate cancer.
... Over the last years, there has been an increased interest in Human Centric Lighting (HCL), which is lighting designed to achieve certain behavioral, visual and biological responses [1]. The biological response to light, which relates to the circadian rhythm, depends on the intrinsically photosensitive retinal ganglion cells (ipRGCs) [2], [3]. Based on the wavelength of the observed light, the ipRGCs extract melanopsin, which significantly influences melatonin extraction [4]. ...
Human centric lighting (HCL) has seen an increase in interest over the last years. The CIE introduced the melanopic efficacy of luminous radiation (MELR), which summarizes the impact of light on melanopsin, a protein that strongly influences melatonin production. In a previous publication, the fundamental spectral limits of MELR in terms of correlated color temperature (CCT) and TM-30 color fidelity have been disclosed. In this paper we extend this study by investigating the spectral MELR boundaries under different Duv constraints. Using the same flexible parametrization for the emission spectrum, we optimize MELR in terms of CCT, and this for different Duv tolerances. The results show that for lower CCT, more stringent Duv constraints result in a significant reduction of the MELR tunability range, while the impact is significantly lower when the CCT increases.
... Light is received by the retina that contains retinal ganglion cells expressing melanopsin or intrinsically photosensitive retinal ganglion cells (ipRGCs), which project through the retinohypothalamic tract to the SCN that then acts by regulating the circadian rhythm (Lockley et al., 2003). In this way, light exposure can delay or advance the circadian clock and alter its normal functioning (Pereira et al., 2022). ...
The circadian rhythm is a nearly 24‐h oscillation found in various physiological processes in the human brain and body that is regulated by environmental and genetic factors. It is responsible for maintaining body homeostasis and it is critical for essential functions, such as metabolic regulation and memory consolidation. Dysregulation in the circadian rhythm can negatively impact human health, resulting in cardiovascular and metabolic diseases, psychiatric disorders, and premature death. Emerging evidence points to a relationship between the dysregulation circadian rhythm and neurodegenerative diseases, suggesting that the alterations in circadian function might play crucial roles in the pathogenesis and progression of neurodegenerative diseases. Better understanding this association is of paramount importance to expand the knowledge on the pathophysiology of neurodegenerative diseases, as well as, to provide potential targets for the development of new interventions based on the dysregulation of circadian rhythm. Here we review the latest findings on dysregulation of circadian rhythm alterations in Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, spinocerebellar ataxia and multiple‐system atrophy, focusing on research published in the last 3 years. image
... Various factors have been shown to influence the non-visual effects of light. For example, the non-visual effects of light have been found to vary with differences in intensity [10][11][12], wavelength [13][14][15], exposure duration [16][17][18], and exposure circadian timing [19,20]. The field of physiological anthropology, which focuses on environmental adaptability, also has a long history of research on the non-visual effects in light environments [21]. ...
Physiological effects of light exposure in humans are diverse. Among them, the circadian rhythm phase shift effect in order to maintain a 24-h cycle of the biological clock is referred to as non-visual effects of light collectively with melatonin suppression and pupillary light reflex. The non-visual effects of light may differ depending on age, and clarifying age-related differences in the non-visual effects of light is important for providing appropriate light environments for people of different ages. Therefore, in various research fields, including physiological anthropology, many studies on the effects of age on non-visual functions have been carried out in older people, children and adolescents by comparing the effects with young adults. However, whether the non-visual effects of light vary depending on age and, if so, what factors contribute to the differences have remained unclear. In this review, results of past and recent studies on age-related differences in the non-visual effects of light are presented and discussed in order to provide clues for answering the question of whether non-visual effects of light actually vary depending on age. Some studies, especially studies focusing on older people, have shown age-related differences in non-visual functions including differences in melatonin suppression, circadian phase shift and pupillary light reflex, while other studies have shown no differences. Studies showing age-related differences in the non-visual effects of light have suspected senile constriction and crystalline lens opacity as factors contributing to the differences, while studies showing no age-related differences have suspected the presence of a compensatory mechanism. Some studies in children and adolescents have shown that children’s non-visual functions may be highly sensitive to light, but the studies comparing with other age groups seem to have been limited. In order to study age-related differences in non-visual effects in detail, comparative studies should be conducted using subjects having a wide range of ages and with as much control as possible for intensity, wavelength component, duration, circadian timing, illumination method of light exposure, and other factors (mydriasis or non-mydriasis, cataracts or not in the older adults, etc.).
... 84 • Limit screen/device time in the hour before bed. Blue screen light suppresses melatonin production 85 and interferes with your circadian rhythms. 86 Even if you use blue-light filters, an upsetting e-mail, deadline reminder, or social media post can heighten your awareness and keep you awake. ...
From homework to exams to proposal deadlines, STEM academia bears many stressors for students, faculty, and administrators. The increasing prevalence of burnout as an occupational phenomenon, along with anxiety, depression, and other mental illnesses in the STEM community is an alarming sign that help is needed. We describe common mental illnesses, identify risk factors, and outline symptoms. We intend to provide guidance on how some people can cope with stressors while also giving advice for those who wish to help their suffering friends, colleagues, or peers. We hope to spark more conversation about this important topic that may affect us all-while also encouraging those who suffer (or have suffered) to share their stories and serve as role models for those who feel they cannot speak.
Although the sensitivity of the circadian system to the characteristics of light (e.g., biological timing, intensity, duration, spectrum) has been well studied in adults, data in early childhood remain limited. Utilizing a crossover, within-subjects design, we examined differences in the circadian response to evening light exposure at two different correlated color temperatures (CCT) in preschool-aged children. Healthy, good sleeping children ( n = 10, 3.0-5.9 years) completed two 10-day protocols. In each protocol, after maintaining a stable sleep schedule for 7 days, a 3-day in-home dim-light circadian assessment was performed. On the first and third evenings of the in-home protocol, dim-light melatonin onset (DLMO) was assessed. On the second evening, children received a 1-h light exposure of 20 lux from either 2700 K (low CCT) or 5000 K (high CCT) (~9 and ~16 melanopic equivalent daylight illuminance (mEDI lux), respectively) centered around their habitual bedtime. Children received the remaining light condition during their second protocol, with the order counterbalanced across participants. Salivary melatonin was collected to compute melatonin suppression and circadian phase shift resulting from each experimental light condition. Melatonin suppression across the 1-h light stimulus was significantly greater during exposure to the high CCT light ( M = 56.3%, SD = 19.25%) than during the low CCT light ( M = 23.90%, SD = 41.06%). Both light conditions resulted in marked delays of circadian timing, but only a small difference ( d = −0.25) was observed in the delay between the 5000 K ( M = 35.3 min, SD = 34.3 min) and 2700 K ( M = 26.7 min, SD = 15.9 min) conditions. Together, these findings add to a growing literature demonstrating high responsivity of the circadian clock to evening light exposure in early childhood and provide preliminary evidence of melatonin suppression sensitivity to differences in light spectrum in preschool-aged children.
Our modern-day lifestyle is frequently accompanied by irregular sleep and eating schedules, shift work, and substantial artificial light exposure at night, leading to chronic circadian disruptions. Aberrations in circadian functioning can cause a myriad of physiological and metabolic irregularities, disturbances in the sleep–wake cycle, neurodegeneration, oxidative damage, and a reduced lifespan. Circadian rhythm, sleep, aging, neurodegeneration, and inflammation form a complex interconnected physiological web. The precise circadian timekeeping system deteriorates as we age, leading to decreased adaptability to environmental changes and disruptions in finely tuned circadian regulations of diverse behavioral, physiological, and metabolic processes. Apparent alterations in sleep patterns also emerge with advancing age, potentially elevating the risk of developing neurodegenerative conditions. Disrupted circadian rhythms and poor sleep can further augment systemic inflammation. Reciprocally, chronic inflammation, in turn, can impact sleep quality, creating a complex feedback loop that may deteriorate age-related neurodegenerative processes. Understanding the intricate relationships between circadian disruption, sleep, aging, neurodegeneration, and inflammation is paramount for devising targeted interventions to promote healthy aging and potentially mitigate the risk of neurodegenerative diseases.
Meredith Bishop, David Ruston, Patricia Martin and John Buch look at the operation and effects of blue light
The circadian clock is a complex cellular mechanism that controls numerous key physiological processes and maintains cellular, tissue, and systemic homeostasis. Disruption of the clock system influences the immune response and brain functions. Immune activation is closely linked with inflammation, neurodegeneration, aging, and other peripheral and central nervous system-related abnormalities. There is increasing evidence that cellular inflammation affects sleep and circadian rhythms and vice-versa. This book offers a structured overview that focuses on the multi-angle interaction of circadian rhythms, sleep, and inflammatory response in normal or pathological conditions.
Background
Patients with migraine often have poor sleep quality between and during migraine attacks. Furthermore, extensive research has identified photophobia as the most common and most bothersome symptom in individuals with migraine, second only to headache. Seeking the comfort of darkness is a common strategy for managing pain during an attack and preventing its recurrence between episodes. Given the well-established effects of daily light exposure on circadian activity rhythms and sleep quality, this study aimed to investigate the relationship between photophobia symptoms and sleep quality in a cohort of patients with migraine.
Methods
A cross-sectional observational study was conducted using existing data extracted from the American Registry for Migraine Research (ARMR). Participants with a migraine diagnosis who had completed the baseline questionnaires (Photosensitivity Assessment Questionnaire (PAQ), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-2 (PHQ-2)), and selected questions of the ARMR Sleep questionnaire were included. Models were created to describe the relationship of photophobia and photophilia with various sleep facets, including sleep quality (SQ), sleep disturbance (SDis), sleep onset latency (SOL), sleep-related impairments (SRI), and insomnia. Each model was controlled for age, sex, headache frequency, anxiety, and depression.
Results
A total of 852 patients meeting the inclusion criteria were included in the analysis (mean age (SD) = 49.8 (13.9), 86.6% (n = 738) female). Those with photophobia exhibited significantly poorer sleep quality compared to patients without photophobia (p < 0.001). Photophobia scores were associated with SQ (p < 0.001), SDis (p < 0.001), SOL (p = 0.011), SRI (p = 0.020), and insomnia (p = 0.005) after controlling for age, sex, headache frequency, depression, and anxiety, signifying that higher levels of photophobia were associated with worse sleep-related outcomes. Conversely, photophilia scores were associated with better sleep-related outcomes for SQ (p < 0.007), SOL (p = 0.010), and insomnia (p = 0.014).
Conclusion
Results suggest that photophobia is a significant predictor of poor sleep quality and sleep disturbances in migraine. These results underscore the necessity for comprehensive and systematic investigations into the intricate interplay between photophobia and sleep to enhance our understanding and develop tailored solutions for individuals with migraine.
Light is an environmental factor that is extrinsic to animals themselves and that exerts a profound influence on the regulation of circadian, neurohormonal, metabolic, and neurobehavioral systems of all animals, including research animals. These widespread biologic effects of light are mediated by distinct photoreceptors—rods and cones that comprise the conventional visual system and melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) of the nonvisual system that interact with the rods and cones. The rods and cones of the visual system, along with the ipRGCs of the nonvisual system, are species distinct in terms of opsins and opsin concentrations and interact with one another to provide vision and regulate circadian rhythms of neurohormonal and neurobehavioral responses to light. Here, we review a brief history of lighting technologies, the nature of light and circadian rhythms, our present understanding of mammalian photoreception, and current industry practices and standards. We also consider the implications of light for vivarium measurement, production, and technological application and provide simple recommendations on artificial lighting for use by regulatory authorities, lighting manufacturers, designers, engineers, researchers, and research animal care staff that ensure best practices for optimizing animal health and well-being and, ultimately, improving scientific outcomes.
Evening exposure to short-wavelength light can affect the circadian clock, sleep and alertness. Intrinsically photosensitive retinal ganglion cells expressing melanopsin are thought to be the primary drivers of these effects. Whether colour-sensitive cones also contribute is unclear. Here, using calibrated silent-substitution changes in light colour along the blue–yellow axis, we investigated whether mechanisms of colour vision affect the human circadian system and sleep. In a 32.5-h repeated within-subjects protocol, 16 healthy participants were exposed to three different light scenarios for 1 h starting 30 min after habitual bedtime: baseline control condition (93.5 photopic lux), intermittently flickering (1 Hz, 30 s on–off) yellow-bright light (123.5 photopic lux) and intermittently flickering blue-dim light (67.0 photopic lux), all calibrated to have equal melanopsin excitation. We did not find conclusive evidence for differences between the three lighting conditions regarding circadian melatonin phase delays, melatonin suppression, subjective sleepiness, psychomotor vigilance or sleep.
The Stage 1 protocol for this Registered Report was accepted in principle on 9 September 2020. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.13050215.v1.
Light has been shown to have a non-visual impact on the biological aspects of human health, particularly on circadian rhythms. Building windows are a potential means of regulating daylight conditions for circadian health and well-being. As a result of advancements in window and glazing technologies and variations in outdoor solar/ sky conditions, understanding daylight's spectral characteristics, which pass through building window systems, is complex. Therefore, a systematic review and summary of the knowledge and evidence available regarding windows' impact on human circadian health is necessary. This study provides an overview of research in this domain, compares approaches and evaluation metrics, and underscores the importance of window parameters' influence on circadian health. Published studies available on various online databases since 2012 were evaluated. The findings of this study define a holistic approach to the melanopic performance of windows and provide an overview of current knowledge regarding the effect of windows on circadian health. Additionally, this work identifies future research directions based on the studies reviewed. This research contributes to the growing body of knowledge on the impact of windows on circadian health, which has implications for the design and construction of buildings in ways that support indoor human health and well-being from the circadian light adequacy perspective.
Introduction . Understanding the peculiarities of perception of color images by patients with achromatopsia helps to identify and differentiate this pathology from diseases with similar clinical symptoms in time. This is becoming increasingly relevant due to ongoing developments in the field of virus vector therapy using an adeno-associated virus carrying the CNGB3 and CNGA3 genes.
Purpose : to investigate the features of perception of color images by patients with achromatopsia, using in addition to the generally accepted developed proprietary tests to quantify the brightness of perceived images.
Materials and methods . Five school-age patients (12–17 years) with complete achromatopsia were observed. The control group included 36 schoolchildren aged from 10 to 17 (av. 13.4 ± 0.5) with a normal state of visual functions. The ophthalmological examination included standard research methods. In children with achromatopsia, OСT data and ERG indicators were taken into account. To study color vision in all children, the following methods were used: E.B. Rabkin’s polychromatic tables, Neitz Test, Farnsworth–Munsell Dichotomodus D-15 Test, a study of the field of vision for white and colored stimuli (on the perimeter of PNR-03). In addition, in children with achromatopsia, the perception of color stimuli with achromatic stimuli was compared using special proprietary images.
Results . Comparison of the results of the study of color vision in patients with achromatopsia in different ways demonstrates the greatest probability of diagnostic errors when using polychromatic tables, which may be due to the ability of these patients to distinguish test figures in some tables based on brightness contrast, rather than contrast of color tones. Increased sensitivity of photoreceptors to short-wave (blue part of the spectrum) radiation and significantly reduced sensitivity to short-wave (red part of the spectrum) in patients with achromatopsia may cause the expansion of the boundaries of the field of view to green and blue stimuli (while the boundaries of the field of view to the blue stimulus almost reach the values for the white stimulus), as well as a significant narrowing to red stimuli compared with the indicators in the control group (p < 0.001). The developed own test images made it possible to quantify the brightness of chromatic stimuli perceived by patients with achromatopsia in comparison with the brightness of achromatic stimuli. The brightest (90–100%) for them was the blue stimulus and practically merged with the white background of the screen. The red stimulus was perceived to be the darkest (minimum brightness). Based on the data obtained, an approximate model of the perception of color images in achromatopsia was created. Conclusion. The obtained data complement the existing ideas about the peculiarities of perception of color images by patients with achromatopsia and can be used to develop new and improve existing methods of diagnosing this disease, as well as to create recommendations for the design of illustrative, educational and advertising material.
The aging effects on circadian rhythms have diverse implications including changes in the pattern of rhythmic expressions, such as a wide fragmentation of the rhythm of rest-activity and decrease in amplitude of activity regulated by the suprachiasmatic nucleus (SCN). The study of blue light on biological aspects has received great current interest due, among some aspects, to its positive effects on psychiatric disorders in humans. This study aims to evaluate the effect of blue light therapy on the SCN functional aspects, through the evaluation of the rest-activity rhythm, in aging rats. For this, 33 sixteen-months-old male Wistar rats underwent continuous records of locomotor activity and were exposed to periods of 6 hours of blue light during the first half of the light phase (Zeitgeber times 0–6) for 14 days. After this, the rats were maintained at 12h:12h light:dark cycle to check the long-term effect of blue light for 14 days. Blue light repeated exposure showed positive effects on the rhythmic variables of locomotor activity in aged rats, particularly the increase in amplitude, elevation of rhythmic robustness, phase advance in acrophase, and greater consolidation of the resting phase. This effect depends on the presence of daily blue light exposure. In conclusion, our results indicate that blue light is a reliable therapy to reduce circadian dysfunctions in aged rats, but other studies assessing how blue light modulates the neural components to modulate this response are still needed.
Study objectives:
A new-type lighting using violet-excitation light-emitting diodes (LED) with an action spectrum centered at approximately 405 nm was developed. Although violet-excitation LEDs can reduce melatonin suppression compared with blue-excitation LEDs, no studies have compared the effects of violet-excitation LEDs with those of blue-excitation LEDs on melatonin suppression. This study was designed to compare the effects of violet-excitation LEDs with those of blue-excitation LEDs on melatonin suppression, psychomotor vigilance, and sleepiness.
Methods:
Sixteen healthy Japanese males aged 20-39 years were exposed to violet- and blue-excitation LEDs for 3 hours in a crossover randomized manner. The primary outcome was changes in salivary melatonin levels compared with the baseline levels. The secondary outcomes were changes in psychomotor vigilance and the Karolinska Sleepiness Scale. Melatonin suppression was calculated from the difference in the area under the curves between the baseline and intervention.
Results:
Of the 16 participants, 15 completed the measurements. The baseline characteristics did not differ significantly between the two groups. After adjusting for age, a difference of 16.28 pg/mL in the mean melatonin suppression was observed between the violet- and blue-excitation LED groups (-2.15 pg/mL vs. -18.43 pg/mL; p = 0.006). The overall melatonin suppression by violet-excitation LEDs was 48.6% smaller than that by blue-excitation LEDs. No significant differences in psychomotor vigilance and sleepiness were observed between the two groups.
Conclusions:
Melatonin suppression in healthy Japanese males exposed to violet-excitation LEDs was significantly smaller than that in those exposed to blue-excitation LEDs. Our preliminary finding indicate that violet-excitation LEDs may have the potential to reduce the magnitude of blue-excitation LED-induced melatonin suppression.
Clinical trial registration:
Registry: Japan Registry of Clinical Trials; Identifier: jRCT 1030200061; Title: Effect of LED light using violet excitation peak on melatonin suppression; URL: https://jrct.niph.go.jp/latest-detail/jRCT1030200061.
In the past decade, the term 'global aging' has gained much attention among researchers, policymakers, civil societies, and governments worldwide. The continuous decline in fertility rates and increased life expectancy have resulted in an ongoing demographic transition where the share of adults aged 65 or older is increasing and outnumbering children younger than five years. In the United States and other developed countries, this rapid demographic transition is expected to continue to strain the existing health infrastructure as it becomes increasingly challenging to ensure healthy living environments for older adults. prepared by experts from gerontology, geriatrics, architectural engineering, and senior living operations to inform and characterize the current continuum of living environments and communities available to older adults. They also identify the common elements that influence the environmental needs of older adults and highlight factors (such as technical assistance, health equity gaps, and caregiver workforce development) that challenge the future of smart and healthy built environments for older adults. A special focus has been placed on contextualizing indoor environmental quality (IEQ) elements and smart building technologies for older individuals, caregivers, and their various requirements (perhaps in their own homes and communities). Together, these viewpoints create a new paradigm to assist in designing and managing intelligent, healthy built environments that respond to human demands. Although this paper focuses on factors in the United States, others can benefit from the framework incubated upon these experiences, making this effort relevant towards addressing global opportunities in environments for older adults.
Regulation of circadian period in humans was thought to differ from that of other species, with the period of the activity
rhythm reported to range from 13 to 65 hours (median 25.2 hours) and the period of the body temperature rhythm reported to
average 25 hours in adulthood, and to shorten with age. However, those observations were based on studies of humans exposed
to light levels sufficient to confound circadian period estimation. Precise estimation of the periods of the endogenous circadian
rhythms of melatonin, core body temperature, and cortisol in healthy young and older individuals living in carefully controlled
lighting conditions has now revealed that the intrinsic period of the human circadian pacemaker averages 24.18 hours in both
age groups, with a tight distribution consistent with other species. These findings have important implications for understanding
the pathophysiology of disrupted sleep in older people.
Complete blindness generally results in the loss of synchronization of circadian rhythms to the 24-hour day and in recurrent insomnia. However, some blind patients maintain circadian entrainment. We undertook this study to determine whether some blind patients' eyes convey sufficient photic information to entrain the hypothalamic circadian pacemaker and suppress melatonin secretion, despite an apparently complete loss of visual function.
We evaluated the input of light to the circadian pacemaker by testing the ability of bright light to decrease plasma melatonin concentrations in 11 blind patients with no conscious perception of light and in 6 normal subjects. We also evaluated circadian entrainment over time in the blind patients.
Plasma melatonin concentrations decreased during exposure to bright light in three sightless patients by an average (+/- SD) of 69 +/- 21 percent and in the normal subjects by an average of 66 +/- 15 percent. When two of these blind patients were tested with their eyes covered during exposure to light, plasma melatonin did not decrease. The three blind patients reported no difficulty sleeping and maintained apparent circadian entrainment to the 24-hour day. Plasma melatonin concentrations did not decrease during exposure to bright light in seven of the remaining blind patients; in the eighth, plasma melatonin was undetectable. These eight patients reported a history of insomnia, and in four the circadian temperature rhythm was not entrained to the 24-hour day.
The visual subsystem that mediates light-induced suppression of melatonin secretion remains functionally intact in some sightless patients. The absence of photic input to the circadian system thus constitutes a distinct form of blindness, associated with periodic insomnia, that afflicts most but not all patients with no conscious perception of light.
The aim of this study was to test if the three cone photopic visual system is the primary ocular photoreceptor input for human circadian regulation by determining the effects of different wavelengths on light-induced melatonin suppression. Healthy subjects with stable sleeping patterns (wake-up time 7:30 AM +/- 12 min) and normal color vision were exposed at night to full-field 505 nm or 555 nm monochromatic stimuli or darkness for 90 min. Plasma collected before and after exposures was quantified for melatonin. Subjects exposed to 10 irradiances at 505 nm showed no significant differences across mean pre-exposure melatonin values (F=0.505). A sigmoidal fluence-response curve fitted to the melatonin suppression data (R(2)=0.97) indicated that 9.34 x 10(12) photons/cm(2)/sec induced a half-saturation response (ED(50)) while 6.84 x 10(13) photons/cm(2)/sec induced a saturation melatonin suppression response. Further, a dose of 4.19 x 10(13) photon/cm(2)/sec at 505 nm was significantly stronger (P < 0.01) than an equal photon dose at 555 nm for melatonin suppression. These data demonstrate that the cone system that mediates human photopic vision is not the primary photoreceptor system to tranduce light stimuli for melatonin regulation.
This work demonstrates that transgenic mice lacking both rod and cone photoreceptors (rd/rd cl) retain a pupillary light reflex (PLR) that does not rely on local iris photoreceptors. These data, combined with previous reports that rodless and coneless mice show circadian and pineal responses to light, suggest that multiple non-image-forming light responses use non-rod, non-cone ocular photoreceptors in mice. An action spectrum for the PLR in rd/rd cl mice demonstrates that over the range 420-625 nm, this response is driven by a single opsin/vitamin A-based photopigment with peak sensitivity around 479 nm (opsin photopigment/OP479). These data represent the first functional characterization of a non-rod, non-cone photoreceptive system in the mammalian CNS.
All known eukaryotic organisms exhibit physiological and behavioral rhythms termed circadian rhythms that cycle with a near-24-hour period; in mammals, light is the most potent stimulus for entraining endogenous rhythms to the daily light cycle. Photic information is transmitted via the retinohypothalamic tract (RHT) to the suprachiasmatic nucleus (SCN) in the hypothalamus, where circadian rhythms are generated, but the retinal photopigment that mediates circadian entrainment has remained elusive. Here we show that most retinal ganglion cells (RGCs) that project to the SCN express the photopigment melanopsin.
Different wavelengths of light were compared for melatonin suppression and phase shifting of the salivary melatonin rhythm. The wavelengths compared were 660 nm (red), 595 nm (amber), 525 nm (green), 497 nm (blue/green), and 470 nm (blue). They were administered with light-emitting diodes equated for irradiance of 130 muW/cm2. Fifteen volunteers participated in all five wavelength conditions and a no light control condition, with each condition conducted over two consecutive evenings. Half-hourly saliva sam ples were collected from 19:00 to 02:00 on night 1 and until 01:00 on night 2. Light was administered for the experimental conditions on the first night only from midnight to 02:00. Percentage melatonin suppression on night 1 and dim light melatonin onset (DLMO) for each night were calculated. The shorter wavelengths of 470, 497, and 525 nm showed the greatest melatonin suppression, 65% to 81%. The shorter wavelengths also showed the greatest DLMO delay on night 2, ranging from 27 to 36 min. The results were consistent with the involvement of a scotopic mechanism in the regulation of circadian phase.
We have discovered an expansive photoreceptive 'net' in the mouse inner retina, visualized by using an antiserum against melanopsin, a likely photopigment. This immunoreactivity is evident in a subset of retinal ganglion cells that morphologically resemble those that project to the suprachiasmatic nucleus (SCN), the site of the primary circadian pacemaker. Our results indicate that this bilayered photoreceptive net is anatomically distinct from the rod and cone photoreceptors of the outer retina, and suggest that it may mediate non-visual photoreceptive tasks such as the regulation of circadian rhythms.
The primary circadian pacemaker, in the suprachiasmatic nucleus (SCN) of the mammalian brain, is photoentrained by light signals
from the eyes through the retinohypothalamic tract. Retinal rod and cone cells are not required for photoentrainment. Recent
evidence suggests that the entraining photoreceptors are retinal ganglion cells (RGCs) that project to the SCN. The visual
pigment for this photoreceptor may be melanopsin, an opsin-like protein whose coding messenger RNA is found in a subset of
mammalian RGCs. By cloning rat melanopsin and generating specific antibodies, we show that melanopsin is present in cell bodies,
dendrites, and proximal axonal segments of a subset of rat RGCs. In mice heterozygous for tau-lacZ targeted to the melanopsin
gene locus, β-galactosidase–positive RGC axons projected to the SCN and other brain nuclei involved in circadian photoentrainment
or the pupillary light reflex. Rat RGCs that exhibited intrinsic photosensitivity invariably expressed melanopsin. Hence,
melanopsin is most likely the visual pigment of phototransducing RGCs that set the circadian clock and initiate other non–image-forming
visual functions.
The master circadian oscillator in the hypothalamic suprachiasmatic nucleus is entrained to the day/night cycle by retinal photoreceptors. Melanopsin (Opn4), an opsin-based photopigment, is a primary candidate for photoreceptor-mediated entrainment. To investigate the functional role of melanopsin in light resetting of the oscillator, we generated melanopsin-null mice (Opn4-/-). These mice entrain to a light/dark cycle and do not exhibit any overt defect in circadian activity rhythms under constant darkness. However, they display severely attenuated phase resetting in response to brief pulses of monochromatic light, highlighting the critical role of melanopsin in circadian photoentrainment in mammals.
Melanopsin has been proposed as an important photoreceptive molecule for the mammalian circadian system. Its importance in this role was tested in melanopsin knockout mice. These mice entrained to a light/dark cycle, phase-shifted after a light pulse, and increased circadian period when light intensity increased. Induction of the immediate-early gene c-fos was observed after a nighttime light pulse in both wild-type and knockout mice. However, the magnitude of these behavioral responses in knockout mice was 40% lower than in wild-type mice. Although melanopsin is not essential for the circadian clock to receive photic input, it contributes significantly to the magnitude of photic responses.
In the mammalian retina, a small subset of retinal ganglion cells (RGCs) are intrinsically photosensitive, express the opsin-like protein melanopsin, and project to brain nuclei involved in non-image-forming visual functions such as pupillary light reflex and circadian photoentrainment. We report that in mice with the melanopsin gene ablated, RGCs retrograde-labeled from the suprachiasmatic nuclei were no longer intrinsically photosensitive, although their number, morphology, and projections were unchanged. These animals showed a pupillary light reflex indistinguishable from that of the wild type at low irradiances, but at high irradiances the reflex was incomplete, a pattern that suggests that the melanopsin-associated system and the classical rod/cone system are complementary in function.
The action spectrum for changing the phase of the rhythm of luminescence in the marine dinoflagellate Gonyaulax polyedra has been determined. Maxima in effectiveness were found at 475 and 650 mmicro. The significance of these findings is discussed.
1. Non-image forming, irradiance-dependent responses mediated by the human eye include synchronisation of the circadian axis and suppression of pineal melatonin production. The retinal photopigment(s) transducing these light responses in humans have not been characterised. 2. Using the ability of light to suppress nocturnal melatonin production, we aimed to investigate its spectral sensitivity and produce an action spectrum. Melatonin suppression was quantified in 22 volunteers in 215 light exposure trials using monochromatic light (30 min pulse administered at circadian time (CT) 16-18) of different wavelengths (lambda(max) 424, 456, 472, 496, 520 and 548 nm) and irradiances (0.7-65.0 microW cm(-2)). 3. At each wavelength, suppression of plasma melatonin increased with increasing irradiance. Irradiance-response curves (IRCs) were fitted and the generated half-maximal responses (IR(50)) were corrected for lens filtering and used to construct an action spectrum. 4. The resulting action spectrum showed unique short-wavelength sensitivity very different from the classical scotopic and photopic visual systems. The lack of fit (r(2) < 0.1) of our action spectrum with the published rod and cone absorption spectra precluded these photoreceptors from having a major role. Cryptochromes 1 and 2 also had a poor fit to the data. Fitting a series of Dartnall nomograms generated for rhodopsin-based photopigments over the lambda(max) range 420-480 nm showed that rhodopsin templates between lambda(max) 457 and 462 nm fitted the data well (r(2) > or =0.73). Of these, the best fit was to the rhodopsin template with lambda(max) 459 nm (r(2) = 0.74). 5. Our data strongly support a primary role for a novel short-wavelength photopigment in light-induced melatonin suppression and provide the first direct evidence of a non-rod, non-cone photoreceptive system in humans.
1.
The spectral sensitivity of the photoreceptors responsible for phase shifting the circadian rhythm of flight activity in the bat,Hipposideros speoris was investigated. For this purpose we studied the phase shifts evoked with 15 min and 2.77 h pulses of monochromatic light at various phases of the rhythm freerunning in DD.
2.
A PRC for the circadian rhythm of flight activity inH. speoris was constructed with white light pulses (1,000 lx for 15 min) against DD background (Fig. 1). In the first set of experiments 15 min monochromatic light pulses of varying intensities were administered to two phases of the rhythm: the phase of the rhythm at which maximal phase advances occur CT 4, and the phase of the rhythm at which maximal phase delays occur CT 18. The intensities of the 15 min monochromatic light pulses required to produce 50% of the phase shifts evoked with white light pulses (1,000 lx for 15 min) at these two phases were determined. The spectral sensitivity curve for advance phase shifts has a maximum at the wavelength 520 nm and the spectral sensitivity curve for delay phase shifts has a maximum at the wavelength 430 nm (Fig. 5).
3.
In the second set of experiments 2.77 h monochromatic light pulses of equal energy of 100 W/cm2 were used. We studied the wavelength dependent phase shifts at four phases of the rhythm: CT 2, CT 4, CT 12 and CT 18. The pulses of 430 and 520 nm evoked unequivocal delay and advance phase shifts, respectively, at all four phases (Fig. 7). These results suggest that at this photopic level of pulse energy, there might be a clear antagonism between the two photoreceptor classes, one having a maximum at the wavelength 430 nm and the other having a maximum at the wavelength 520 nm.
4.
We suggest that there may exist two different classes of photoreceptors in the retinas ofH. speoris. The S photoreceptors (short wavelength sensitive) having a maximum at the wavelength 430 nm and the M photoreceptors (middle wavelength sensitive) having a maximum at the wavelength 520 nm that mediate delay and advance phase shifts, respectively.
The daily rhythm in body temperature in rats was continuously monitored during exposure to low-intensity environmental illumination of various colors in the visible and near-ultraviolet spectrum. The ability of phase shifts in the lighting schedule to induce concomitant changes in the rhythm was used to determine the spectral sensitivity of the retinal photoreceptor systems mediating rhythm entrainment. Green light (lambda = 530 +/- 45 nanometers) was most potent, and red (lambda = 660 +/- 19 nanometers) and ultraviolet (lambda = 360 +/- 34 nanometers) were least potent in entraining the temperature rhythm.
Environmental light cycles are the dominant synchronizers of circadian rhythms in the field, and artificial light cycles and pulses are the major tools used in the laboratory to analyse properties of circadian systems. It is therefore surprising that few studies have analysed the physical parameters of light stimuli that affect circadian rhythms. There have previously been no spectral sensitivity measurements for phase shifting the circadian rhythms of mammals and only two preliminary reports on the wavelength dependence of this response exist. Using the magnitude of phase shift caused by a single 15-min pulse of monochromatic light given 6 h after activity onset, we have now characterized the spectral sensitivity of the photoreceptors responsible for phase shifting the locomotor rhythm of the hamster (Mesocricetus auratus). The sensitivity curve for this response has a maximum near 500 nm and is similar to the absorption spectrum for rhodopsin. Although the spectral sensitivity is consistent with a rhodopsin-based photopigment, two features of the photoreceptive system that mediates entrainment are unusual: the threshold of the response is high, especially for a predominantly rod retina like that of the hamster, and the reciprocal relationship between intensity and duration holds for extremely long durations (up to 45 min). These results suggest that the photoreceptive system mediating entrainment is markedly different from that involved in visual image formation.
The purpose of this study was to test the capacity of different visible wavelengths of light to suppress nocturnal levels of pineal melatonin in hamsters. It was found that the visible wavelengths vary in their ability to perturb pineal melatonin. During the period of peak pineal melatonin production, animals were exposed to fluorescent light sources having half-peak bandwidths of 339-371 nm (near-ultraviolet), 435-500 nm (blue), 510-550 nm (green), 558-636 nm (yellow) and 653-668 nm (red). In each experiment, animals were exposed to equal irradiances of each light source. The different irradiances used were 0.928, 0.200, 0.186, 0.074 and 0.019 microW/cm2. The resultant data demonstrated that blue fluorescent light was the most efficient in suppressing pineal melatonin. Green fluorescent light was found to be the next most efficient light for inhibiting pineal melatonin followed by yellow fluorescent light. Near-ultraviolet and red light were the least capable of suppressing pineal melatonin. These observations suggest that the retinal photopigment responsible for mediating the pineal gland's response to light in the hamster may be either rhodopsin or another blue-sensitive chromophore.
In this report we have characterized the photopigments mediating circadian phase shifts in retinal degenerate (rd) mice. In aged rd/rd mice, which lack detectable opsin, high performance liquid chromatography (HPLC) was used to quantify the photopigment chromophore 11-cis-retinaldehyde. This chromophore was photoisomerized in whole eyes, suggesting the presence of a functional opsin-based photopigment system. We also analyzed the spectral sensitivity of phase shifting circadian locomotor rhythms. Our data implicate a photopigment that is consistent with the involvement of the middle wavelength-sensitive cone photoreceptors (M-cones; lambda(max) = 511 nm) found in the mouse retina. In addition, discrete near-ultraviolet (UV-A) pulses were capable of eliciting large phase shifts in circadian locomotor activity rhythms. This result is consistent with the involvement of the short wavelength-sensitive cone photoreceptors (UV-cones; lambda(max) = 359 nm) in photoentrainment. Collectively, these data suggest that both cone classes of the mouse may mediate the photic regulation of circadian rhythms. If this is the case, circadian sensitivity can be maintained by very few degenerate cones. Alternatively, an unknown class of ocular photoreceptor may fulfill this function.
Despite the preeminence of light as the synchronizer of the circadian timing system, the phototransductive machinery in mammals which transmits photic information from the retina to the hypothalamic circadian pacemaker remains largely undefined. To determine the class of photopigments which this phototransductive system uses, we exposed a group (n = 7) of human subjects to red light below the sensitivity threshold of a scotopic (i.e. rhodopsin/rod-based) system, yet of sufficient strength to activate a photopic (i.e. cone-based) system. Exposure to this light stimulus was sufficient to reset significantly the human circadian pacemaker, indicating that the cone pigments which mediate color vision can also mediate circadian vision.
The purpose of this review was to discuss the influence of light on humans in the environment, focusing the relation between the quality of light and human biological rhythms, and also to apply the results on lighting planning to a living space which takes into account human health and comfort. The main discussions were as follows: 1) The effects of light on the behavior of core temperature and melatonin vary depending on its wavelength. Light with long wavelengths, such as light with a low color temperature and red light, had little influence on the human biological rhythms. On the other hand, green and blue light--light of mid-short wavelength such as light with a high color temperature--had a greater influence. 2) From the relation between the stimulus received by each photoreceptor and the inhibition of core temperature and melatonin, it might be concluded that the photoreceptor responsible for transmitting light information that affects biological rhythms is M-cones. 3) A higher light intensity was required in the morning than in the evening to induce the inhibition of melatonin secretion. This result suggests the possibility of existence of a diurnal change of sensitivity of the photoreceptors (M-cones). 4) From all these results, it is proposed in the field of living environment and living engineering that light with a low color temperature should be used for low-level lighting at night, and high-level light with a high color temperature in the morning.
We have examined the responses of neurones in the suprachiasmatic nuclei (SCN) of the rat to retinal illumination under photopic and scotopic conditions to identify the types of photoreceptor input to these nuclei.
The majority of visually responsive SCN neurones studied under dark adaptation received rod input (48 of 52, 92 %). The action spectrum conformed to the sensitivity of rhodopsin, with maximal sensitivity at around 505 nm.
When also studied under light adaptation, most visually responsive SCN neurones (20 out of 26, 77 %) responded to input from cones. The action spectra conformed to the spectrum of green cone opsin, with a main sensitivity peak at 510 nm and a significant secondary peak in the near‐ultraviolet region of the spectrum.
The frequency of spontaneous activity was typically low under scotopic conditions (range 0.2‐17.2 Hz) and higher under photopic conditions (range 0.6‐40 Hz) for any given neurone. The most common response under scotopic conditions was an ‘on‐excitation’ (32 of 48, 62.5 %), which changed under photopic conditions to an on‐excitation followed by a more prominent off‐inhibition.
Responses also changed due to endogenous ultradian cycles. Depending on the phase, responses could be altogether absent and even reverted from excitation to inhibition on opposite phases of a cycle. Ultradian cycles had a circadian dependence and were most common at around the light phase:dark phase (L:D) and D:L transition points of the circadian cycle.
Under photopic conditions, SCN neurones showed rhythmic electrical activity, with a preferred firing interval that had a value between 18 and 39 ms. This rhythmic activity was probably the result of endogenous subthreshold membrane potential oscillations.
In conclusion, light acting either via rod or cone pathways could have powerful, opposing actions on SCN neurones. These actions were state dependent. The presence of these neuronal responses suggests a role for rod and cone photoreceptors in SCN function.
Circadian rhythms are oscillations in the biochemical, physiological, and behavioral functions of organisms that occur with a periodicity of approximately 24 h. They are generated by a molecular clock that is synchronized with the solar day by environmental photic input. The cryptochromes are the mammalian circadian photoreceptors. They absorb light and transmit the electromagnetic signal to the molecular clock using a pterin and flavin adenine dinucleotide (FAD) as chromophore/cofactors, and are evolutionarily conserved and structurally related to the DNA repair enzyme photolyase. Humans and mice have two cryptochrome genes, CRY1 and CRY2, that are differentially expressed in the retina relative to the opsin-based visual photoreceptors. CRY1 is highly expressed with circadian periodicity in the mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN). Mutant mice lacking either Cry1 or Cry2 have impaired light induction of the clock gene mPer1 and have abnormally short or long intrinsic periods, respectively. The double mutant has normal vision but is defective in mPer1 induction by light and lacks molecular and behavioral rhythmicity in constant darkness. Thus, cryptochromes are photoreceptors and central components of the molecular clock. Genetic evidence also shows that cryptochromes are circadian photoreceptors in Drosophila and Arabidopsis, raising the possibility that they may be universal circadian photoreceptors. Research on cryptochromes may provide new understanding of human diseases such as seasonal affective disorder and delayed sleep phase syndrome.
Light synchronizes mammalian circadian rhythms with environmental time by modulating retinal input to the circadian pacemaker—the
suprachiasmatic nucleus (SCN) of the hypothalamus. Such photic entrainment requires neither rods nor cones, the only known
retinal photoreceptors. Here, we show that retinal ganglion cells innervating the SCN are intrinsically photosensitive. Unlike
other ganglion cells, they depolarized in response to light even when all synaptic input from rods and cones was blocked.
The sensitivity, spectral tuning, and slow kinetics of this light response matched those of the photic entrainment mechanism,
suggesting that these ganglion cells may be the primary photoreceptors for this system.
The mammalian eye shows marked adaptations to time of day. Some of these modifications are not acute responses to short-term light exposure but rely upon assessments of the photic environment made over several hours. In the past, all attempts at a mechanistic understanding have assumed that these adaptations originate with light detection by one or other of the classical photoreceptor cells (rods or cones). However, previous work has demonstrated that the mammalian eye contains non-rod, non-cone photoreceptors. This study aimed to determine whether such photoreceptors contribute to retinal adaptation.
In the human retina, second-order processing of signals originating in cones takes significantly longer at night than during the day. Long-term light exposure at night is capable of reversing this effect. Here, we employed the cone ERG as a tool to examine the properties of the irradiance measurement pathway driving this reversal. Our findings indicate that this pathway (1) integrates irradiance measures over time periods ranging from at least 15 to 120 min; (2) responds to relatively bright light, having a dynamic range almost entirely outside the sensitivity of rods; (3) acts on the cone pathway primarily through a local retinal mechanism; and (4) detects light via an opsin:vitamin A photopigment (lambda(max) approximately 483 nm).
A photopigment with a spectral sensitivity profile quite different from those of the classical rod and cone opsins but matching the standard profile of an opsin:vitamin A-based pigment drives adaptations of the human primary cone visual pathway according to time of day.
Human adult males were exposed to combinations of two illuminances and two broadband spectral power distributions over the course of four night-time sessions. Results showed that melatonin suppression is dominated by short visible wavelengths (420-520 nm), consistent with recently published studies. Although the authors of these recent studies suggest that a novel opsin underlies melatonin suppression, the present paper offers a more conservative interpretation of the data based on what is known about existing photoreceptors and associated neuroanatomy and neurophysiology.
Research over the past decade has provided overwhelming evidence that photoreception in the vertebrate eye is not confined to the rod and cone photoreceptors. It appears that photoreceptor cells within the inner retina provide irradiance information to a wide variety of different photosensory tasks including photoentrainment, pupillary constriction and masking behaviour. Action spectra in mice lacking all rod and cone photoreceptors ( rd/rd cl) have demonstrated the existence of a previously uncharacterised, opsin/vitamin-A-based photopigment with peak sensitivity at 479 nm (opsin photopigment/OP(479)). The review addresses the question: has the gene encoding OP(479) already been isolated, and if not, what type of gene should we be seeking and where in the eye might this gene be expressed? On the basis of available data, the gene that encodes OP(479) remains unidentified, and two broad possibilities exist. On the assumption that OP(479) will be like all of the other vertebrate photopigments (ocular and extraocular) and share a close phylogenetic relationship based upon amino acid identity and a conserved genomic structure, then the gene encoding OP(479) has yet to be isolated. Alternatively, there may have been a separate line of photopigment evolution in the vertebrates that has given rise to the melanopsin family. If true then the mammalian melanopsin gene may encode OP(479). Only when melanopsin and other candidates for OP(479) have been functionally expressed, and shown to encode a photopigment that matches the action spectrum of OP(479), can firm conclusions about the identity of the non-rod, non-cone ocular photoreceptor of mammals be made.
Ocular light exposure patterns are the primary stimuli for entraining the human circadian system to the local 24-h day. Many totally blind persons cannot use these stimuli and, therefore, have circadian rhythms that are not entrained. However, a few otherwise totally blind persons retain the ability to suppress plasma melatonin concentrations after ocular light exposure, probably using a neural pathway that includes the site of the human circadian pacemaker, suggesting that light information is reaching this site. To test definitively whether ocular light exposure could affect the circadian pacemaker of some blind persons and whether melatonin suppression in response to bright light correlates with light-induced phase shifts of thecircadian system, the authorsperformed experiments with 5 totally blind volunteers using a protocol known to induce phase shifts of the circadian pacemaker in sighted individuals. In the 2 blind individuals who maintained light-induced melatonin suppression, the circadian system was shifted by appropriately timed bright-light stimuli. These data demonstrate that light can affect the circadian pacemaker of some totally blind individuals--either by altering the phase of the circadian pacemaker or by affecting its amplitude. They are consistent with data from animal studies demonstrating that there are different neural pathways and retinal cells that relay photic information to the brain: one for conscious light perception and the other for non-image-forming functions.
Neurons in the mammalian suprachiasmatic nucleus (SCN), the principal pacemaker of the circadian system, receive direct retinal input. Some SCN neurons respond to retinal illumination or optic nerve stimulation with changes in firing rates. In nocturnal rodents, retinal illumination increases firing rates of a large majority and decreases firing rates of a minority of responsive neurons. In two species of diurnal rodent, these proportions are altered or even reversed. Since retinal input to the SCN has been reported to involve release of the excitatory neurotransmitter glutamate, the mechanism mediating suppressions is unknown. We studied responses of neurons in SCN slices from diurnal degus and nocturnal rats to optic nerve stimulation. To test whether suppressions are mediated indirectly by release of the inhibitory neurotransmitter GABA from SCN neurons that are first activated by glutamate release, we attempted to block suppressions by adding to the bath either APV, an antagonist for excitatory glutamate receptors, or bicuculline, a GABA(A) receptor antagonist. If glutamate is the only neurotransmitter released by optic nerves in the SCN, APV should prevent both activations and suppressions in response to optic nerve stimulation. We found that APV had little effect on suppressions although it effectively blocked activations. Bicuculline blocked most suppressions. These findings are inconsistent with a model in which the retina provides only excitatory glutamate input to the SCN via NMDA receptors. Since some retinal fibers in adult mammals contain GABA, it is possible that the retinal innervation of the SCN includes both glutamate- and GABA-containing axons.