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 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...

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Published in	The Journal of neuroscience Vol. 21; no. 16; pp. 6405 - 6412
Main Authors	Brainard, George C, Hanifin, John P, Greeson, Jeffrey M, Byrne, Brenda, Glickman, Gena, Gerner, Edward, Rollag, Mark D
Format	Journal Article
Language	English
Published	Legacy CDMS Soc Neuroscience 15.08.2001 Society for Neuroscience
Subjects	Adolescent Adult Circadian Rhythm - physiology Circadian Rhythm - radiation effects Dose-Response Relationship, Radiation Eye - drug effects Eye - metabolism Eye - radiation effects Female Humans Life Sciences (General) Light Male Melatonin - blood Mydriatics - administration & dosage Photic Stimulation - instrumentation Photic Stimulation - methods Photoreceptor Cells, Vertebrate - classification Photoreceptor Cells, Vertebrate - metabolism Photoreceptor Cells, Vertebrate - radiation effects Rod Opsins - biosynthesis Rod Opsins - classification Time Factors Support, U.s. Gov't, Non-P.h.s Human Clinical Trial Opsin/biosynthesis/classification Support, U.s. Gov't, P.h.s Non-Nasa Center Photoreceptors, Vertebrate/classification/metabolism/radiation Effects Male Mydriatics/administration & Dosage Time Factors Photic Stimulation/instrumentation/methods Nasa Discipline Regulatory Physiology Light Adolescent Eye/drug Effects/metabolism/radiation Effects Adult Female Melatonin/blood Dose-Response Relationship, Radiation Circadian Rhythm/physiology/radiation Effects NASA Discipline Regulatory Physiology Non-NASA Center
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Abstract	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 (R(2) = 0.81-0.95). The action spectrum constructed from these data fit an opsin template (R(2) = 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.
AbstractList	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 (R(2) = 0.81-0.95). The action spectrum constructed from these data fit an opsin template (R(2) = 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.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 (R(2) = 0.81-0.95). The action spectrum constructed from these data fit an opsin template (R(2) = 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. 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 (R(2) = 0.81-0.95). The action spectrum constructed from these data fit an opsin template (R(2) = 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. 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 ( R 2 = 0.81–0.95). The action spectrum constructed from these data fit an opsin template ( R 2 = 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. 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 plus or minus 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 (R super(2) = 0.81-0.95). The action spectrum constructed from these data fit an opsin template (R super(2) = 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.
Audience	PUBLIC
Author	Glickman, Gena Greeson, Jeffrey M Hanifin, John P Rollag, Mark D Byrne, Brenda Brainard, George C Gerner, Edward
AuthorAffiliation	2 Department of Anatomy, Physiology and Genetics, Uniformed Services University of Health Sciences, Bethesda, Maryland 20814 1 Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and
AuthorAffiliation_xml	– name: 1 Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and – name: 2 Department of Anatomy, Physiology and Genetics, Uniformed Services University of Health Sciences, Bethesda, Maryland 20814
Author_xml	– sequence: 1 fullname: Brainard, George C – sequence: 2 fullname: Hanifin, John P – sequence: 3 fullname: Greeson, Jeffrey M – sequence: 4 fullname: Byrne, Brenda – sequence: 5 fullname: Glickman, Gena – sequence: 6 fullname: Gerner, Edward – sequence: 7 fullname: Rollag, Mark D
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/11487664$$D View this record in MEDLINE/PubMed
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Snippet	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...
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SubjectTerms	Adolescent Adult Circadian Rhythm - physiology Circadian Rhythm - radiation effects Dose-Response Relationship, Radiation Eye - drug effects Eye - metabolism Eye - radiation effects Female Humans Life Sciences (General) Light Male Melatonin - blood Mydriatics - administration & dosage Photic Stimulation - instrumentation Photic Stimulation - methods Photoreceptor Cells, Vertebrate - classification Photoreceptor Cells, Vertebrate - metabolism Photoreceptor Cells, Vertebrate - radiation effects Rod Opsins - biosynthesis Rod Opsins - classification Time Factors
Title	Action Spectrum for Melatonin Regulation in Humans: Evidence for a Novel Circadian Photoreceptor
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