Demonstration of additivity failure in human circadian phototransduction.
ABSTRACT Published data, both on nocturnal melatonin suppression in humans and on widely accepted retinal structure and function, suggest that spectral opponency plays a role in human circadian phototransduction. We directly test subadditivity, implied by spectral opponency, in human circadian phototransduction in response to nearly monochromatic and to polychromatic light.
Adult male human subjects were exposed for 60 minutes to two intensities each of two lighting conditions, during nighttime experimental sessions. One condition consisted of light from mercury vapor lamps (450 and 1050 lx), and one condition consisted of light from these lamps filtered such that only the spectral line from this lamp at 436 nm was presented to subjects (7.5 and 15 lx).
Melatonin suppression from the filtered illumination at 436 nm alone was greater than mercury lamp illumination (containing energy at 436 nm in addition to other wavelengths), even when the sources exposed subjects' retinae to equal amounts of irradiance at 436 nm.
This direct test of subadditivity, together with evidence from neuroanatomy, supports the inference that spectral opponency is a fundamental characteristic of human circadian phototransduction.
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ABSTRACT: In humans, modulation of circadian rhythms by light is thought to be mediated primarily by melanopsin-containing retinal ganglion cells, not rods or cones. Melanopsin cells are intrinsically blue light-sensitive but also receive input from visual photoreceptors. We therefore tested in humans whether cone photoreceptors contribute to the regulation of circadian and neuroendocrine light responses. Dose-response curves for melatonin suppression and circadian phase resetting were constructed in subjects exposed to blue (460 nm) or green (555 nm) light near the onset of nocturnal melatonin secretion. At the beginning of the intervention, 555-nm light was equally effective as 460-nm light at suppressing melatonin, suggesting a significant contribution from the three-cone visual system (lambda(max) = 555 nm). During the light exposure, however, the spectral sensitivity to 555-nm light decayed exponentially relative to 460-nm light. For phase-resetting responses, the effects of exposure to low-irradiance 555-nm light were too large relative to 460-nm light to be explained solely by the activation of melanopsin. Our findings suggest that cone photoreceptors contribute substantially to nonvisual responses at the beginning of a light exposure and at low irradiances, whereas melanopsin appears to be the primary circadian photopigment in response to long-duration light exposure and at high irradiances. These results suggest that light therapy for sleep disorders and other indications might be optimized by stimulating both photoreceptor systems.Science translational medicine 05/2010; 2(31):31ra33. · 10.76 Impact Factor
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ABSTRACT: There is a growing interest in the role that light plays on nocturnal melatonin production and, perhaps thereby, the incidence of breast cancer in modern societies. The direct causal relationships in this logical chain have not, however, been fully established and the weakest link is an inability to quantitatively specify architectural lighting as a stimulus for the circadian system. The purpose of the present paper is to draw attention to this weakness. We reviewed the literature on the relationship between melatonin, light at night, and cancer risk in humans and tumor growth in animals. More specifically, we focused on the impact of light on nocturnal melatonin suppression in humans and on the applicability of these data to women in real-life situations. Photometric measurement data from the lighted environment of women at work and at home is also reported. The literature review and measurement data demonstrate that more quantitative knowledge is needed about circadian light exposures actually experienced by women and girls in modern societies. Without such quantitative knowledge, limited insights can be gained about the causal relationship between melatonin and the etiology of breast cancer from epidemiological studies and from parametric studies using animal models.Journal of Carcinogenesis 02/2006; 5:20.
Article: Circadian light.[Show abstract] [Hide abstract]
ABSTRACT: The present paper reflects a work in progress toward a definition of circadian light, one that should be informed by the thoughtful, century-old evolution of our present definition of light as a stimulus for the human visual system. This work in progress is based upon the functional relationship between optical radiation and its effects on nocturnal melatonin suppression, in large part because the basic data are available in the literature. Discussed here are the fundamental differences between responses by the visual and circadian systems to optical radiation. Brief reviews of photometry, colorimetry, and brightness perception are presented as a foundation for the discussion of circadian light. Finally, circadian light (CLA) and circadian stimulus (CS) calculation procedures based on a published mathematical model of human circadian phototransduction are presented with an example.Journal of Circadian Rhythms 02/2010; 8(1):2.