ArticlePDF Available

Mitochondrial Mechanisms of Photobiomodulation in Context of New Data About Multiple Roles of ATP

DOI: 10.1089/pho.2010.2789
Authors:
Tiina Karu at Laser Technology Research Center of Russian Academy of Science, Moscow, Russia
Tiina Karu
  • Laser Technology Research Center of Russian Academy of Science, Moscow, Russia
Download full-text PDF
Read full-text
Download citation
Content uploaded by Tiina Karu
Author content
All content in this area was uploaded by Tiina Karu on May 10, 2014
Content may be subject to copyright.
Guest Editorial
Mitochondrial Mechanisms of Photobiomodulation
in Context of New Data About Multiple Roles of ATP
Tiina Karu, Dr. Sci., Ph.D.
Various cellular responses to visible and IR-A radia-
tion have been studied for decades in the context of
molecular mechanisms of laser phototherapy [also called
photobiomodulation, low-level light therapy (LLLT)]. LLLT
uses monochromatic and quasimonochromatic light in the
optical region of *600–1,000 nm to treat in a nondestructive
and nonthermal fashion various soft-tissue and neurologic
conditions.
1
This modality also was recently used to reverse
toxic effects of neurotoxins, to treat strokes and acute myo-
cardial infarction, and to stimulate stem cell proliferation.
2
This multiplicity of conditions treated with photo-
biomodulation has persuaded many unbelievers of the value
of such an universal method.
3
It is generally accepted that the mitochondria are the ini-
tial site of light action in cells, and cytochrome coxidase (the
terminal enzyme of the mitochondrial respiratory chain) is
the responsible molecule.
2–8
Mixed-valence copper compo-
nents of cytochrome coxidase, Cu
A
and Cu
B
, are believed to
be the photoacceptors.
5,9,10
The same photoacceptor mole-
cule for different cellular responses can explain, at least
partly, the versatility of low-power laser effects.
The excitation of the photoacceptor molecule sets in mo-
tion cellular metabolism through cascades of reactions called
cellular signaling
2,3
or retrograde mitochondrial signaling.
11
At least two reactions are starting points for monitoring
cellular-signaling reactions after light action on the cyto-
chrome coxidase molecule. One of them is dissociation of
NO from the catalytic center of cytochrome coxidase.
12,13
Spectroscopic studies of irradiated cellular monolayer
show that two charge-transfer channels putatively to
CuAred and CuBoxid , as well as two reaction channels puta-
tively connected with d-d transition in CuBred and CuAoxid
chromophores, are reorganized dependent on NO presence
or absence.
9
It has been suggested that the dissociation of NO
(a physiologic regulator of cytochrome coxidase activity)
rearranges downstream signaling effects.
14
Another signaling pathway starting from the mitochon-
dria is connected with ATP. The ATP extrasynthesis in iso-
lated mitochondria and intact cells of various types, under
irradiation with light of different wavelengths, is well
documented.
2
ATP is a universal fuel inside living cells that
drives all biologic reactions. It is known that even small
changes in the ATP level can significantly alter cellular me-
tabolism. Increasing the amount of this energy may improve
the cellular metabolism, especially in suppressed or other-
wise ill cells.
7,8
In connection with the versatility of LLLT effects, I draw
the readers’ attention to a comparatively new aspect of the
ATP molecule. A long series of discoveries has demonstrated
that ATP is not only an energy currency inside cells, but it is
also a critical signaling molecule that allows cells and tissues
throughout the body to communicate with one another.
15
This new aspect of ATP as an intercellular signaling molecule
allows broadening the understanding of universality phe-
nomenon of LLLT as well. It is known now that neurons
release ATP into muscle, gut, and bladder tissue as a mes-
senger molecule. The specific receptors for ATP as the sig-
naling molecule (P2 family) and for its final breakdown
product, adenosine (P1 family), were found and identi-
fied.
15,16
ATP activation of P2 receptors (subtypes P2X and P2Y)
can produce different cellular effects. A recent article by
Anders et al.
17
demonstrated that P2Y2 and P2Y11 receptors
were expressed in the irradiated at l¼810-nm normal
human neural progenitor cells in vitro. It appeared that the
irradiation could be used as a replacement for growth fac-
tors. This line of research opens a new understanding of the
complicated mechanisms of LLLT. From the point of view of
the topic of the present article, the role of ATP as a signaling
molecule provides a new basis for explaining the versatility
of LLLT effects.
The second important point in connection with multiple
functions of ATP and P2X and P2Y receptors is the following.
When bound by ATP, P2X receptors form a channel that
allows sodium and calcium ions to enter the cells. ATP
binding to the extracellular surface of P2Y receptors starts a
cascade of molecular interactions inside cells, with those re-
sulting in intracellular calcium stores being released.
16
The
increase in intracellular Ca
2þ
ions ([Ca
2þ
]
i
) due to the irra-
diation has been measured by many authors,
2
but the
mechanism of the phenomenon of [Ca
2þ
]
i
increase in the ir-
radiated cells has not been explained. Ca
2þ
is a global posi-
tive effector of mitochondrial function, and thus, any
perturbation in mitochondrial or cytosolic Ca
2þ
homeostasis
will have implications on mitochondrial functions. This
concerns the regulation of [Ca
2þ
]
i
from outside by binding
ATP to P2X receptors. It is important to remember that both
Ca
2þ
uptake and efflux from mitochondria consume DC
m
Institute of Laser and Information Technologies of Russian Academy of Sciences, Troitsk, Moscow region, Russian Federation.
Photomedicine and Laser Surgery
Volume 28, Number 2, 2010
ªMary Ann Liebert, Inc.
Pp. 159–160
DOI: 10.1089=pho.2010.2789
159
and, in this way, depend on mitochondrial activity (and
therefore on ATP synthesis), which can be regulated by
irradiation.
Understanding of the multiple role of ATP in cellular
metabolism will also provide a better appreciation of the cel-
lular and molecular mechanisms of LLLT. A recent review
16
indicates that laboratories worldwide are now racing to turn
the data about ATP as a neurotransmitter into therapies. As a
neurotransmitter, ATP is directly involved in brain function,
sensory reception, and the neuron system control of muscles
and organs. When released by nonneuronal cells, it often
triggers protective responses, such as bone building and cell
proliferation.
15,16
Even a very brief look at all the conditions
in the human body in which ATP is now believed to play a
role as the signaling molecule,
16
and comparison of these
data with the data on the versatile clinical actions of LLLT
1
provides grounds for a new way of thinking.
First, chronic and neuropathic pains are the disorders
treated successfully with LLLT for many years.
1,18
ATP sig-
naling is believed to be involved into pain therapy.
19
Second, it is proposed that acupuncture (mechanical de-
formation of the skin by needles and application of heat or
electrical current) leads to release of large amounts of ATP
from keratinocytes, fibroblasts, and other cells in the skin.
20
Recall that acupuncture by laser light is a well-known
modality.
1
Third, the tumor-killing action of the photobiomodulation
technique has been documented
21
but met with skepticism.
1
A tumor-killing effect of ATP has been described.
22
Perhaps it is now time to reconsider the skepticism about
treating tumors with LLLT, taking into account that ATP
signaling acts, in part, to promote the suicide of the tumor
cells and, in part, to promote cell differentiation, which slows
tumor cell proliferation.
22
This offers grounds to hope that the new data about the
multiple functions of ATP help to bring the LLLT method
closer to mainstream medicine.
References
1. Tuner, J., and Hode, L. (2002). Laser Therapy. Clinical Practice
and Scientific Background. Gra
¨ngesberg, Sweden: Prima
Books AB.
2. Karu, T. (2007). Ten Lectures on Basic Science of Laser Photo-
therapy. Gra
¨ngesberg, Sweden: Prima Books AB.
3. Karu, T. (2003). Low power laser therapy, in: Biomedical
Photonics Handbook. Vo-Dinh, T. (ed). Boca Raton: CRC Press,
pp. 48-1–48-25.
4. Kato, M., Shinizawa, K., and Yoshikawa, S. (1981). Cyto-
chrome oxidase is a possible photoreceptor in mitochondria.
Photobiochem. Photobiophys. 2, 263–269.
5. Karu, T.I., and Afanasyeva, N.I. (1995). Cytochrome c oxi-
dase acts as a primary photoacceptor in cell cultures sub-
jected to visible and near IR laser irradiation. Doklady
Biochemistry (Moscow) 342, 84–86.
6. Pastore, D., Greco, M., and Passarella, S. (2000). Specific
He-Ne laser sensitivity of the purified cytochrome c oxidase.
Int. J. Radiat. Biol. 76, 863–870.
7. Wong-Riley, M.T., Liang, H.L., Eells, J.T., et al. (2005). Pho-
tobiomodulation directly benefits primary neurons func-
tionally inactivated by toxins: role of cytochrome c oxidase.
J. Biol. Chem. 280, 4761–4771.
8. Eells, J., Wong-Riley, M.T., VerHoeve, J., et al. (2004). Mi-
tochondrial signal introduction in accelerated wound and
retinal healing by near-infrared light therapy. Mitochon-
drion 4, 559–567.
9. Karu, T.I., Pyatibrat, L.V., Kolyakov, S.F., and Afanasyeva,
N.I. (2005). Absorption measurements of a cell monolayer
relevant to phototherapy: reduction of cytochrome c oxidase
under near IR radiation. J. Photochem. Photobiol. B: Biol. 81,
98–106.
10. Karu, T.I., Pyatibrat, L.V., Kolyakov, S.F., and Afanasyeva,
N.I. (2008). Absorption measurements of cell monolayers
relevant to mechanisms of laser phototherapy: reduction or
oxidation of cytochrome c oxidase under laser radiation at
632.8 nm. Photomed. Laser Surg. 26, 593–599.
11. Karu, T.I. (2008). Mitochondrial signaling in mammalian
cells activated by red and near IR radiation. Photochem.
Photobiol. 84, 1091–1099.
12. Karu, T.I., Pyatibrat, L.V., and Afanasyeva, N.I. (2004).
A novel mitochondrial signaling pathway activated by
visible-to-near infrared radiation. Photochem. Photobiol.
80, 366372.
13. Sarti, P., Giuffre, A., Barone, M.C., et al. (2003). Nitric oxide
and cytochrome c oxidase: reaction mechanisms from the
enzyme to the cell. Free Radic. Biol. Med. 34, 509–520.
14. Lane, N. (2006). Power games. Nature 443, 901–903.
15. Burnstock, G. (2009). Purines and sensory nerves. Exp.
Pharmacol. 194, 332–392.
16. Khakh, B.S., and Burnstock, G. (2009). The double life of
ATP. Sci. Am. 12, 84–92.
17. Anders, J.J., Romanczyk, T.B., Ilev, I.K., et al. (2008). Light
supports neurite outgrowth of human neural progenitor
cells in vitro: the role of P2Y receptors. IEEE J. Select. Topics
Quant. Electr. 14, 118–125.
18. Chow, R.T., Johnson, H.I., Lopes-Martins, R.A.B., and Bjor-
dal, J.M. (2010). Efficacy of low-level laser therapy in the
management of neck pain: a systematic review and meta-
analysis of randomised placebo or active-treatment con-
trolled trials. The Lancet (online Now. 13, 2009. www.
thelancet.com).
19. Burnstock, G. (2009). Purinergic receptors and pain. Curr.
Pharm. Des. 15, 1717–1735.
20. Burmstock, G. (2009). Acupuncture: a novel hypothesis for
the involvement of purinergic signaling. Med. Hypoth. 73,
470–472.
21. Mikhailov, V.A. Skobelkin, O.K., Denisov, I.N., et al. (1993).
Investigations on the influence of low level diode laser
irradiation of the growth of experimental tumors. Laser
Ther. 5, 33–38.
22. Shabbir, M., Ryten, H., Thompson, C., et al. (2007). Pur-
inergic receptor-mediated effects of ATP in high-grade
bladder cancer. BJU Intern. 101, 106–112.
Address correspondence to:
Prof. Tiina Karu, Dr. Sci., Ph.D.
Institute of Laser and Information Technologies
of Russian Academy of Sciences, Troitsk,
Moscow region 142190, Russian Federation
E-mail: tkaru@isan.troitsk.ru
160 GUEST EDITORIAL
This article has been cited by:
... PBM is a non-thermal process involving endogenous chromophores eliciting photophysical (i.e., linear and nonlinear) and photochemical events at various physiological levels [8]. The most popular mechanism for PBM effects involves its actions on mitochondrial metabolism, cell membrane photoreceptors or transporters, and activation of extracellular latent growth factor, TGF-1 [9,10,[15][16][17][18][19][20][21][22][23][24][25]. Most applications of PBM focus on the local effects on tissue that is directly exposed to far-red or NIR light. ...
... This is the most accepted mechanism of action, and it is based on photons being absorbed by cytochromes, which are present inside the mitochondria either as functional proteins or as electron transport shuttles (i.e., cytochrome c oxidase, CCO). This leads to an increased production of ATP, increased oxygen consumption, raised mitochondrial membrane potential, and increased mitochondrial biogenesis, which have all been shown in vitro after PBM, resulting in transient increase in ATP, ROS, and NO levels [9,20,21,59,67]. Mitochondrial dysfunction is thought to be a causal factor in the detrimental health effects of sleep deficits, especially in people who are late chronotypes [30,31]. ...
Effects of Near-Infrared Light on Well-Being and Health in Human Subjects with Mild Sleep-Related Complaints: A Double-Blind, Randomized, Placebo-Controlled Study
Article
Full-text available
  • Dec 2022
Modern urban human activities are largely restricted to the indoors, deprived of direct sunlight containing visible and near-infrared (NIR) wavelengths at high irradiance levels. Therapeutic exposure to doses of red and NIR, known as photobiomodulation (PBM), has been effective for a broad range of conditions. In a double-blind, randomized, placebo-controlled study, we aimed to assess the effects of a PBM home set-up on various aspects of well-being, health, sleep, and circadian rhythms in healthy human subjects with mild sleep complaints. The effects of three NIR light (850 nm) doses (1, 4, or 6.5 J·cm−2) were examined against the placebo. Exposure was presented five days per week between 9:30 am and 12:30 pm for four consecutive weeks. The study was conducted in both summer and winter to include seasonal variation. The results showed PBM treatment only at 6.5 J·cm−2 to have consistent positive benefits on well-being and health, specifically improving mood, reducing drowsiness, reducing IFN-γ, and resting heart rate. This was only observed in winter. No significant effects on sleep or circadian rhythms were noted. This study provides further evidence that adequate exposure to NIR, especially during low sunlight conditions, such as in the winter, can be beneficial for human health and wellness.
View
... The proposal that red and near-infrared wavelengths may promote melatonin synthesis in mitochondria via the pathway involving nitric oxide and enhanced activity of soluble adenylyl cyclase further bolsters the synergistic relationship between light and melatonin [218,219]. The ability to increase adenosine triphosphate (ATP) production in mitochondria is one of the most widely accepted mechanisms behind the effectiveness of photobiomodulation in dementia and other health challenges [211,217,[220][221][222]. The fact that both infrared light and melatonin increase ATP production, and the adenosine moiety of ATP which is structurally similar to melatonin is capable of solubilizing protein aggregation point to the existence of a most unexpected, dynamic relationship between NIR light and melatonin that is inextricably connected to the regulation of hydrogen bonds, viscosity, protein hydration, and protein aggregation ( Figure 1). ...
Light, Water, and Melatonin: The Synergistic Regulation of Phase Separation in Dementia
Article
Full-text available
The swift rise in acceptance of molecular principles defining phase separation by a broad array of scientific disciplines is shadowed by increasing discoveries linking phase separation to pathological aggregations associated with numerous neurodegenerative disorders, including Alzheimer's disease, that contribute to dementia. Phase separation is powered by multivalent macromolecular interactions. Importantly, the release of water molecules from protein hydration shells into bulk creates entropic gains that promote phase separation and the subsequent generation of insoluble cytotoxic aggregates that drive healthy brain cells into diseased states. Higher viscosity in interfacial waters and limited hydration in interiors of biomolecular condensates facilitate phase separation. Light, water, and melatonin constitute an ancient synergy that ensures adequate protein hydration to prevent aberrant phase separation. The 670 nm visible red wavelength found in sunlight and employed in photobiomodulation reduces interfacial and mitochondrial matrix viscosity to enhance ATP production via increasing ATP synthase motor efficiency. Melatonin is a potent antioxidant that lowers viscosity to increase ATP by scavenging excess reactive oxygen species and free radicals. Reduced viscosity by light and melatonin elevates the availability of free water molecules that allow melatonin to adopt favorable conformations that enhance intrinsic features, including binding interactions with adenosine that reinforces the adenosine moiety effect of ATP responsible for preventing water removal that causes hydrophobic collapse and aggregation in phase separation. Precise recalibration of interspecies melatonin dosages that account for differences in metabolic rates and bioavailability will ensure the efficacious reinstatement of the once-powerful ancient synergy between light, water, and melatonin in a modern world.
View
... This enzyme is located in the outer membrane of the mitochondria, and, when activated, catalyses the electron transfer from cytochrome c to oxygen, while reducing oxygen into water. This results in the production of protons, which in turn activates adenosine triphosphate (ATP) synthase, thus increasing ATP production (Hamblin 2017;Karu 2010;Wong-Riley et al. 2005). A secondary mechanism would involve a dissociation of nitric oxide from CCO, which, when bounded, inhibits cellular respiration by competing with oxygen binding. ...
A systematic review of the effects of transcranial photobiomodulation on brain activity in humans
Article
In recent years, transcranial photobiomodulation (tPBM) has been developing as a promising method to protect and repair brain tissues against damages. The aim of our systematic review is to examine the results available in the literature concerning the efficacy of tPBM in changing brain activity in humans, either in healthy individuals, or in patients with neurological diseases. Four databases were screened for references containing terms encompassing photobiomodulation, brain activity, brain imaging, and human. We also analysed the quality of the included studies using validated tools. Results in healthy subjects showed that even after a single session, tPBM can be effective in influencing brain activity. In particular, the different transcranial approaches - using a focal stimulation or helmet for global brain stimulation - seemed to act at both the vascular level by increasing regional cerebral blood flow (rCBF) and at the neural level by changing the activity of the neurons. In addition, studies also showed that even a focal stimulation was sufficient to induce a global change in functional connectivity across brain networks. Results in patients with neurological disease were sparser; nevertheless, they indicated that tPBM could improve rCBF and functional connectivity in several regions. Our systematic review also highlighted the heterogeneity in the methods and results generated, together with the need for more randomised controlled trials in patients with neurological diseases. In summary, tPBM could be a promising method to act on brain function, but more consistency is needed in order appreciate fully the underlying mechanisms and the precise outcomes.
View
... This can result from signaling pathways that originate from photon absorption, the opening of transient receptor potential channels of the vanilloid type, membrane receptors including tyrosine kinases, and diversity of photoactive molecules designated as opsins (41,42). The measurements of NOx and ATP were based on evidence that these molecules have a key role in signaling pathways of cell adherence and metabolism as a response to the PBM (43,44). Both NOx and ATP levels were increased after three 4 J cm À2 irradiations. ...
Light‐Emitting Diode Can Enhance the Metabolism and Paracrine Action of Mesenchymal Stem Cells
Article
Full-text available
This study investigated the influence of red light‐emitting diodes (LED, 630 nm) on different irradiation parameters and the number of applications on mesenchymal stem cells derived from adipose tissue (AdMSCs) metabolism and paracrine factors. The AdMSCs were irradiated with a LEDbox device (output power: 2452.5 mW; laser beam: 163.5 cm2; irradiance: 15 mW/cm2) using radiant exposures of 0.5, 2, and 4 J/cm2, respectively. AdMSCs were irradiated once or every 48 h up to three irradiations. All molecular analyses were performed 24 hours after the last irradiation. LED did not induce changes in cell count, DNA damage, and oxidative stress. A significant repercussion of the LED has been noticed after three irradiations with 4 J/cm2. AdMSCs had higher levels of IL‐6, IGF‐1, and NOx index. A higher ATP content and MMT/Resazurin assay were identified in AdMSCs irradiated three times with 4 J/cm2. Mitochondrial basal respiration, maximal respiration and proton leak under metabolic stress were reduced by 0.5 and 2 J/cm2 irradiations. These data showed that three LED irradiations with 4 J/cm2 may be a suitable parameter for future AdMSCs therapy because of its improved metabolic activity, ATP content, and IL‐6, IGF‐1, and nitric oxide secretion.
View
... 24 Both red and amber wavelengths are absorbed by the chromophore, cytochrome c oxidase, which has been considered as one of the main photon-absorbing molecules that mediate the effects of PBM. 25,26 However, red light penetrates the deeper layers of the skin. 27,28 Nam et al. 18 compared red and amber PBM for skin rejuvenation, but the device for applying amber light was polychromatic (411-777 nm, with a central wavelength of 594 nm). ...
Photobiomodulation Reduces Periocular Wrinkle Volume by 30%: A Randomized Controlled Trial
Article
  • Feb 2023
Objective: This study aimed to evaluate red and amber light-emitting diode protocols for facial rejuvenation at the same light dose. Background: The demand for minimally invasive cosmetic procedures to address skin aging has grown throughout the world. In vitro red and amber photobiomodulation (PBM) has been shown to improve collagen synthesis. Meanwhile, red PBM has already been studied in clinical trials; however, a comparison of the use of different wavelengths at the same light dose to reduce periocular wrinkles has not yet been performed. Methods: This split-face, randomized clinical trial recruited 137 women (40-65 years old) presenting with skin phototypes II-IV and Glogau photoaging scale types II-IV. The individuals received 10 sessions for 4 weeks of red (660 nm) and amber (590 nm) PBM (3.8 J/cm2), one at each side of the face. The outcomes, measured before and after the treatments, were the periocular wrinkle volume measured by VisioFace® RD equipment; hydration measured by the Corneometer CM 825; skin elasticity measured by the Cutometer Dual MPA 580; and quality of life determined by adapted versions of validated questionnaires [Melasma Quality of Life Scale-Brazilian Portuguese (MelasQoL-BP) and Skindex-29]. Results: There was a significant reduction in wrinkle volume after red (31.6%) and amber (29.9%) PBM. None of the treatments improved skin hydration and viscoelasticity. Both questionnaires showed improvements in participants' quality of life. Conclusions: PBM, both at red and amber wavelengths, is an effective tool for rejuvenation, producing a 30% wrinkle volume reduction. The technique has strong potential in patients with diabetes or those presenting with keloids, conditions for which highly inflammatory rejuvenating procedures are not indicated. Clinical trial registration number: REBEC-6YFCBM.
View
... Thus, laser therapy is more effective for injured or destructed tissues than sound tissues. 5 Laser irradiation stimulates intracellular and tissue elements and enhances cell proliferation and regeneration. Induction and activation of DNA and RNA, enhanced cell oxygen uptake, stimulation of enzymes, mitochondrial activity, increased level of cytochrome oxidase, and increased ATP synthesis are among the other effects of LLLs. ...
The Effect of Low-Level Laser Therapy on the Viability of Human Dental Pulp Stem Cells
Article
  • Dec 2022
Introduction: This study assessed the effect of low-level laser (LLL) irradiation on the viability of dental pulp stem cells (DPSCs). Methods: In this in vitro experimental study, human DPSCs were purchased from the cell bank of Iranian Genetic Resources and cultured in flasks containing Dulbecco's modified Eagle's medium supplemented with 20% fetal bovine serum (FBS) at 37°C, 5% CO2, and 95% humidity. The cells were stored in semi-confluent form, and the culture medium was refreshed every two days. The cells in the control group were not laser-irradiated, but the cells in the experimental groups were irradiated with 660-nm and 808-nm diode lasers with 4.1 J/cm2 energy density. Cell viability was assessed at baseline and after 24, 48, and 72 hours using the methyl thiazolyl tetrazolium (MTT) assay. The effects of laser irradiation, laser wavelength, and time on the percentage of cell viability were analyzed by two-way ANOVA and Tukey's test. Results: The effects of laser irradiation and its wavelength (P=0.04), time of assessment (P<0.001), and the interaction effect of group and time (P=0.02) on cell viability were significant. Cell viability in 660-nm and 808-nm laser groups at 48 and 72 hours was higher than that of the control group; however, only the difference in cell viability between the 660-nm laser group and the control group at 72 hours was statistically significant (P=0.03). Conclusion: Considering the optimal effect of diode laser irradiation (particularly 660 nm) on the viability of DPSCs, we conclude that it may be suitable for relevant clinical applications.
View
... The use of photobiomodulation is based on the fact that the cells present sensitive receptor systems to the photons, and these, once stimulated by radiation, promote changes in the permeability of the cell membrane, in the transmembrane transport systems, besides stimulating mitochondrial enzymes, such as cytochrome c oxidase, which results in increased production of ATP [27,28]. Also, histological and morphometric analyses demonstrate that treatment with LEd induces a qualitative and quantitative increase in fibroblasts, thereby raising the content of tissue collagen [29]. ...
View
... The enzyme cytochrome C oxidase (CCO), referred to as complex four in the respiratory electron transport chain (ETC), has been identified as the major photoacceptor underlying the mechanism of action for PBM. A multitude of benefits are observed following treatment with PBM that parallel the molecular underpinnings contributing to non-exudative AMD pathology including inflammatory and mitochondrial distress [3][4][5][6]. Mitochondrial activation at CCO elicited by PBM enhances ETC function and promotes adenosine triphosphate (ATP) production, the cell's major source of energy. PBM can also modulate intracellular signaling molecules, such as reactive-oxygen species (ROS) and nitric oxide (NO) production and, by extrapolation, ROS-and NO-activated signaling pathways involving NfkB activation and cell death that subserve pleotropic signaling cascades that modulate multiple downstream events to effect sustained changes in cell function and viability. ...
LIGHTSITE II Randomized Multicenter Trial: Evaluation of Multiwavelength Photobiomodulation in Non-exudative Age-Related Macular Degeneration
Article
Full-text available
  • Jan 2023
Abstract Introduction Photobiomodulation (PBM) represents a potential treatment for non-exudative age-related macular degeneration (AMD). PBM uses wavelengths of light to target components of the mitochondrial respiratory chain to improve cellular bioenergetic outputs. The aim of this study was to further investigate the effects of PBM on clinical, quality of life (QoL) and anatomical outcomes in subjects with intermediate stage non-exudative AMD. Methods The multicenter LIGHTSITE II study was a randomized clinical trial evaluating safety and efficacy of PBM in intermediate non-exudative AMD. The LumiThera Valeda® Light Delivery System delivered multiwavelength PBM (590, 660 and 850 nm) or sham treatment 3 × per week over 3–4 weeks (9 treatments per series) with repeated treatments at baseline (BL), 4 and 8 months. Subjects were enrolled with 20/32 to 20/100 best-corrected visual acuity (BCVA) and no central geographic atrophy (GA) within the central fovea (500 μm). Results LIGHTSITE II enrolled 44 non-exudative AMD subjects (53 eyes). PBM-treated eyes showed statistically significant improvement in BCVA at 9 months (n = 32 eyes, p = 0.02) with a 4-letter gain in the PBM-treated group versus a 0.5-letter gain in the sham-treated group (ns, p
View
Use of a colorimeter is a viable method to measure melanin and erythema content in the context of laser beam attenuation by use of a class IV laser in different tissues in dogs
Article
  • Mar 2023
Objective: Patient factors may alter laser photon attenuation, but these factors have not been adequately evaluated in live dogs. Our objective was to evaluate class IV laser beam attenuation (LBA) by canine tissues using a colorimeter to evaluate melanin and erythema indices. We hypothesized that greater melanin and erythema indices and unclipped hair would increase LBA, and these properties would vary among tissues. Animals: 20 client-owned dogs. Procedures: Between October 1 and December 1, 2017, colorimeter measurements and LBA in various tissues before and after clipping overlying hair were evaluated. Data were analyzed using generalized linear mixed models. Statistical significance was set at P < .05. Results: LBA was greater in unclipped (98.6 ± 0.4%) than clipped hair (94.6 ± 0.4%). The least LBA occurred in the pinna (93%) while the greatest occurred in the caudal vertebra (100%) and caudal semitendinosis muscles (100%). Each mm of tissue thickness resulted in LBA of 11.6%. Each unit increase in melanin index resulted in a 3.3% increase in LBA. There was no association of LBA with erythema index. Clinical relevance: To our knowledge, this is the first study that evaluated LBA by different tissues in live dogs using a colorimeter to evaluate melanin and erythema indices. We recommend clipping hair prior to photobiomodulation to decrease laser beam attenuation and using increased laser doses in thicker tissues and dogs with high melanin content. The colorimeter may be helpful in customizing patient treatment dosimetry. Future studies are necessary to determine therapeutic laser doses for adequate photobiomodulation effects.
View
Effect of light needle in the treatment of opioid use disorder: A protocol for a randomized controlled trial
Article
Opioid use disorder occurs worldwide and creates an increasing economic burden and public health crisis. Some problems are associated with using opioid agonists; therefore, there is a need to develop non-opioid treatments to improve acute and long-term opioid withdrawal syndromes. We will enroll 100 participants with opioid use disorders receiving methadone maintenance treatment at an addiction treatment center and randomly allocate them to an experimental or control group. The experimental group will receive 12 sessions of light needle therapy within 4 weeks, while the control group will receive sham light needle treatment without any laser output. Urinary morphine levels were assessed before and after treatment. Participants will be asked to self-report their number of episodes or days of heroin use and heroin craving/refusal to use heroin in the previous week before and after treatment on a visual analogue scale score of 0 to 10. Quality of life will be reported using the Short Form-12v2 before and after 4 weeks of treatment. Pulse diagnosis and heart rate variability will be evaluated before and after treatment. Baseline patient characteristics will be compared between the groups using the independent t test and the χ2 test. Data between the 2 groups will be compared using generalized estimation equations, and paired t tests. This study aims to investigate the effect of adjuvant light needle therapy in patients with opioid use disorder on methadone maintenance treatment.
View
View
Low-Power Laser Therapy
Chapter
  • Mar 2003
The first publications about low-power laser therapy (then called laser biostimulation) appeared more than 30 years ago. Since then, approximately 2000 studies have been published on this still controversial topic. In the 1960s and 1970s, doctors in Eastern Europe, and especially in the Soviet Union and Hungary, actively developed laser biostimulation. However, scientists around the world harbored an open skepticism about the credibility of studies stating that low-intensity visible-laser radiation acts directly on an organism at the molecular level. The coherence of laser radiation for achieving stimulative effects on biological objects was more than suspect. Supporters in Western countries, such as Italy, France, and Spain, as well as in Japan and China also adopted and developed this method, but the method was — and still remains — outside mainstream medicine. The controversial points of laser biostimulation, which were topics of great interest at that time, were analyzed in reviews that appeared in the late 1980s.
View
View
Investigations on the influence of low level diode laser irradiation on the growth of experimental tumours
Article
  • Jan 1993
Investigations on rats with an implanted tumour-carcinosarcoma of Walker (26 animals), cancer of the mammary glands, RMK-1 (75 animals) and in mice with spontaneous cancer of the mammary gland (188 animals)-have shown that the application of a low-level diode laser beam (890 nm) can effect the growth of the experimental tumour. Minimal doses produce a tumouro-static effect, while other doses produce different effects. Low level laser irradiation promotes dystrophic and necrotic changes in tumoural nodes.
View
Cytochrome c oxidase acts as a primary photoacceptor in cell cultures subjected to visible and near IR laser irradiation
Article
  • May 1995
Low-power laser radiation of visible and near IR spectral ranges is widely used in clinical practice to treat wounds and ulcers of various etiologies. However, there are only a few works devoted to photobiological studies of the effect of light of these spectral ranges on the metabolism of nonphotosynthesizing cells. Our results suggested that the light absorbance by certain chromophores of cytochrome c oxidase alters the extent of oxidation of these chromophores, i.e., affects the rate (and, probably, the mechanism) of electron transfer within the molecule. Based on previous results and the data obtained, we suggest that these reactions are related to the molecular mechanism of the low-power laser therapy at the level of a single cell. 15 refs., 1 fig.
View
Mitochondrial Signaling in Mammalian Cells Activated by Red and Near-IR Radiation
Article
Mitochondrial signaling is an information channel between the mitochondrial respiratory chain and the nucleus for the transduction signals regarding the functional state of the mitochondria. The present review examines the question whether radiation of visible and near-IR (IR-A) radiation can activate this retrograde-type cellular signaling pathway. Experimental data about modulation of elements of mitochondrial retrograde signaling by the irradiation (mitochondrial membrane potential DeltaPsi(m), reactive oxygen species ROS, Ca(2+), NO, pH(i), fission-fusion homeostasis of mitochondria) are reviewed. The terminal enzyme of the mitochondrial respiratory chain cytochrome c oxidase is considered as the photoacceptor. Functions of cytochrome c oxidase as a signal generator as well as a signal transducer in irradiated cells are outlined.
View
The double life of ATP
Article
  • Dec 2009
The molecule ATP, famous as an essential energy source inside cells, also carries critical messages between cells. That dual role is suggesting fresh ideas for fighting human diseases
View
Efficacy of low-level laser therapy in the management of neck pain: a systematic review and meta-analysis of randomised placebo or active-treatment controlled trials
Article
Neck pain is a common and costly condition for which pharmacological management has limited evidence of efficacy and side-effects. Low-level laser therapy (LLLT) is a relatively uncommon, non-invasive treatment for neck pain, in which non-thermal laser irradiation is applied to sites of pain. We did a systematic review and meta-analysis of randomised controlled trials to assess the efficacy of LLLT in neck pain. We searched computerised databases comparing efficacy of LLLT using any wavelength with placebo or with active control in acute or chronic neck pain. Effect size for the primary outcome, pain intensity, was defined as a pooled estimate of mean difference in change in mm on 100 mm visual analogue scale. We identified 16 randomised controlled trials including a total of 820 patients. In acute neck pain, results of two trials showed a relative risk (RR) of 1.69 (95% CI 1.22-2.33) for pain improvement of LLLT versus placebo. Five trials of chronic neck pain reporting categorical data showed an RR for pain improvement of 4.05 (2.74-5.98) of LLLT. Patients in 11 trials reporting changes in visual analogue scale had pain intensity reduced by 19.86 mm (10.04-29.68). Seven trials provided follow-up data for 1-22 weeks after completion of treatment, with short-term pain relief persisting in the medium term with a reduction of 22.07 mm (17.42-26.72). Side-effects from LLLT were mild and not different from those of placebo. We show that LLLT reduces pain immediately after treatment in acute neck pain and up to 22 weeks after completion of treatment in patients with chronic neck pain. None.
View
Purines and Sensory Nerves
Article
P2X and P2Y nucleotide receptors are described on sensory neurons and their peripheral and central terminals in dorsal root, nodose, trigeminal, petrosal, retinal and enteric ganglia. Peripheral terminals are activated by ATP released from local cells by mechanical deformation, hypoxia or various local agents in the carotid body, lung, gut, bladder, inner ear, eye, nasal organ, taste buds, skin, muscle and joints mediating reflex responses and nociception. Purinergic receptors on fibres in the dorsal spinal cord and brain stem are involved in reflex control of visceral and cardiovascular activity, as well as relaying nociceptive impulses to pain centres. Purinergic mechanisms are enhanced in inflammatory conditions and may be involved in migraine, pain, diseases of the special senses, bladder and gut, and the possibility that they are also implicated in arthritis, respiratory disorders and some central nervous system disorders is discussed. Finally, the development and evolution of purinergic sensory mechanisms are considered.
View
Acupuncture: A novel hypothesis for the involvement of purinergic signalling
Article
  • Aug 2009
The hypothesis is summarised schematically in Fig. 1. It is proposed that mechanical deformation of the skin by needles and application of heat or electrical current leads to release of large amounts of ATP from keratinocytes, fibroblasts and other cells in skin; the ATP then occupies specific receptor subtypes expressed on sensory nerve endings in the skin and tongue; the sensory nerves send impulses through ganglia to the spinal cord, the brain stem, hypothalamus and higher centres; the brain stem and hypothalamus contain neurons that control autonomic functions, including cardiovascular, gastrointestinal, respiratory, urinogenital and musculo-skeletal activity. Impulses generated in sensory fibres in the skin connect with interneurons to modulate (either inhibition or facilitation) the activities of the motoneurons in the brain stem and hypothalamus to change autonomic functions; specifically activated sensory nerves, via interneurons, also inhibit the neural pathways to the pain centres in the cortex.
View