Action spectrum for melatonin regulation in humans: Evidence for a novel circadian photoreceptor

The photopigment in the human eye that transduces light for circadian and n euroendocrine regulation, is unknown. The aim of this study was to establis h an action spectrum for light-induced melatonin suppression that could hel p elucidate the ocular photoreceptor system for regulating the human pineal gland. Subjects (37 females, 35 males, mean age of 24.5 +/- 0.3 years) wer e healthy and had normal color vision. Full-field, monochromatic light expo sures took place between 2:00 and 3:30 A.M. while subjects' pupils were dil ated. Blood samples collected before and after light exposures were quantif ied for melatonin. Each subject was tested with at least seven different ir radiances of one wavelength with a minimum of 1 week between each nighttime exposure. Nighttime melatonin suppression tests (n = 627) were completed w ith wavelengths from 420 to 600 nm. The data were fit to eight univariant, sigmoidal fluence-response curves (R-2 = 0.81-0.95). The action spectrum co nstructed from these data fit an opsin template (R-2 = 0.91), which identif ies 446-477 nm as the most potent wavelength region providing circadian inp ut for regulating melatonin secretion. The results suggest that, in humans, a single photopigment may be primarily responsible for melatonin suppressi on, and its peak absorbance appears to be distinct from that of rod and con e cell photopigments for vision. The data also suggest that this new photop igment is retinaldehyde based. These findings suggest that there is a novel opsin photopigment in the human eye that mediates circadian photoreception .