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The Journal of Neuroscience, August 15, 2001, 21(16):6405-6412

Action Spectrum for Melatonin Regulation in Humans: Evidence for a Novel Circadian Photoreceptor

George C. Brainard1, John P. Hanifin1, Jeffrey M. Greeson1, Brenda Byrne1, Gena Glickman1, Edward Gerner1, and Mark D. Rollag2

1 Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and 2 Department of Anatomy, Physiology and Genetics, Uniformed Services University of Health Sciences, Bethesda, Maryland 20814

The photopigment in the human eye that transduces light for circadian and neuroendocrine regulation, is unknown. The aim of this study was to establish an action spectrum for light-induced melatonin suppression that could help elucidate the ocular photoreceptor system for regulating the human pineal gland. Subjects (37 females, 35 males, mean age of 24.5 ± 0.3 years) were healthy and had normal color vision. Full-field, monochromatic light exposures took place between 2:00 and 3:30 A.M. while subjects' pupils were dilated. Blood samples collected before and after light exposures were quantified for melatonin. Each subject was tested with at least seven different irradiances of one wavelength with a minimum of 1 week between each nighttime exposure. Nighttime melatonin suppression tests (n = 627) were completed with wavelengths from 420 to 600 nm. The data were fit to eight univariant, sigmoidal fluence-response curves (R2 = 0.81-0.95). The action spectrum constructed from these data fit an opsin template (R2 = 0.91), which identifies 446-477 nm as the most potent wavelength region providing circadian input for regulating melatonin secretion. The results suggest that, in humans, a single photopigment may be primarily responsible for melatonin suppression, and its peak absorbance appears to be distinct from that of rod and cone cell photopigments for vision. The data also suggest that this new photopigment is retinaldehyde based. These findings suggest that there is a novel opsin photopigment in the human eye that mediates circadian photoreception.

Key words: melatonin; action spectrum; circadian; wavelength; light; pineal gland; neuroendocrine; photoreception; photopigment; human


Copyright © 2001 Society for Neuroscience  0270-6474/01/21166405-08$05.00/0


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