Spectral Responses of the Human Circadian System Depend on the Irradiance and Duration of Exposure to Light

May 14, 2010Science translational medicine

How the human body clock responds to light depends on its brightness and length of exposure

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Abstract

Exposure to 555-nm light was equally effective as 460-nm light at suppressing melatonin at the onset of nocturnal secretion.

Cone photoreceptors may significantly contribute to the regulation of melatonin suppression and circadian phase resetting.
The effectiveness of 555-nm light diminished over time compared to 460-nm light during exposure.
At low irradiances, the influence of 555-nm light on phase resetting was greater than what could be accounted for by melanopsin activation alone.
Melanopsin is suggested to be the primary photopigment for circadian responses during prolonged light exposure at high irradiances.
Combining stimulation of both melanopsin and cone photoreceptors could enhance light therapy for sleep disorders.

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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.

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Spectral Responses of the Human Circadian System Depend on the Irradiance and Duration of Exposure to Light

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