A Novel Human Opsin in the Inner Retina
Open accessAbstract
Here we report the identification of a novel human opsin, melanopsin, that is expressed in cells of the mammalian inner retina. The human melanopsin gene consists of 10 exons and is mapped to chromosome 10q22. This chromosomal localization and gene structure differs significantly from that of other human opsins that typically have four to seven exons. A survey of 26 anatomical sites indicates that, in humans, melanopsin is expressed only in the eye.In situ hybridization histochemistry shows that melanopsin expression is restricted to cells within the ganglion and amacrine cell layers of the primate and murine retinas. Notably, expression is not observed in retinal photoreceptor cells, the opsin-containing cells of the outer retina that initiate vision. The unique inner retinal localization of melanopsin suggests that it is not involved in image formation but rather may mediate nonvisual photoreceptive tasks, such as the regulation of circadian rhythms and the acute suppression of pineal melatonin. The anatomical distribution of melanopsin-positive retinal cells is similar to the pattern of cells known to project from the retina to the suprachiasmatic nuclei of the hypothalamus, a primary circadian pacemaker.
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Photoreceptor cells containing melanopsin play a role in the phase-shifting effects of short-wavelength light.
“Photoreceptor cells containing melanopsin play a role in the phase-shifting effects of short-wavelength light.”
Cites
Melanopsin: An opsin in melanophores, brain, and eye
Provencio, I., Jiang, G., De Grip, W. J., Hayes, W. P., & Rollag, M. D. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.1.340 · Cited by 975 · see citing works
Self-citationA novel Go-mediated phototransduction cascade in scallop visual cells
Kojima, D., Terakita, A., Ishikawa, T., Tsukahara, Y., Maeda, A., & Shichida, Y. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.37.22979 · Cited by 198 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Coordination of circadian timing in mammals
Reppert, S. M., & Weaver, D. R. (2002) · Nature · doi:10.1038/nature00965 · Cited by 4,379 · see citing works
Phototransduction by retinal ganglion cells that set the circadian clock
Berson, D. M., Dunn, F. A., & Takao, M. (2002) · Science · doi:10.1126/science.1067262 · Cited by 3,629 · see citing works
Dibner, C., Schibler, U., & Albrecht, U. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135821 · Cited by 2,421 · see citing works
Action Spectrum for Melatonin Regulation in Humans: Evidence for a Novel Circadian Photoreceptor
Brainard, G. C., Hanifin, J. P., Greeson, J. M., Byrne, B., Glickman, G., Gerner, E., & Rollag, M. D. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-16-06405.2001 · Cited by 1,930 · see citing works
Self-citationMolecular analysis of mammalian circadian rhythms
Reppert, S. M., & Weaver, D. R. (2001) · Annual Review of Physiology · doi:10.1146/annurev.physiol.63.1.647 · Cited by 1,444 · see citing works
Dacey, D. M., Liao, H.-W., Peterson, B. B., Robinson, F. R., Smith, V. C., Pokorny, J., Yau, K.-W., & Gamlin, P. D. (2005) · Nature · doi:10.1038/nature03387 · Cited by 1,333 · see citing works
Thapan, K., Arendt, J., & Skene, D. J. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.t01-1-00261.x · Cited by 1,320 · see citing works
Measuring and using light in the melanopsin age
Lucas, R. J., Peirson, S. N., Berson, D. M., Brown, T. M., Cooper, H. M., Czeisler, C. A., Figueiro, M. G., Gamlin, P. D., Lockley, S. W., O’Hagan, J. B., et al. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2013.10.004 · Cited by 1,278 · see citing works
Self-citationHattar, S., Lucas, R. J., Mrosovsky, N., Thompson, S., Douglas, R. H., Hankins, M. W., Lem, J., Biel, M., Hofmann, F., Foster, R. G., et al. (2003) · Nature · doi:10.1038/nature01761 · Cited by 1,245 · see citing works
Zeitzer, J. M., Dijk, D., Kronauer, R. E., Brown, E. N., & Czeisler, C. A. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.00695.x · Cited by 1,175 · see citing works
Light as a central modulator of circadian rhythms, sleep and affect
LeGates, T. A., Fernandez, D. C., & Hattar, S. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3743 · Cited by 1,001 · see citing works
Central projections of melanopsin‐expressing retinal ganglion cells in the mouse
Hattar, S., Kumar, M., Park, A., Tong, P., Tung, J., Yau, K., & Berson, D. M. (2006) · Journal of Comparative Neurology · doi:10.1002/cne.20970 · Cited by 996 · see citing works
Cajochen, C., Münch, M., Kobialka, S., Kräuchi, K., Steiner, R., Oelhafen, P., Orgül, S., & Wirz-Justice, A. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-0957 · Cited by 939 · see citing works
The Neurobiology of Sleep: Genetics, cellular physiology and subcortical networks
Pace-Schott, E. F., & Hobson, J. A. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn895 · Cited by 937 · see citing works
Melanopsin ( <i>Opn4</i> ) Requirement for Normal Light-Induced Circadian Phase Shifting
Panda, S., Sato, T. K., Castrucci, A. M., Rollag, M. D., DeGrip, W. J., Hogenesch, J. B., Provencio, I., & Kay, S. A. (2002) · Science · doi:10.1126/science.1076848 · Cited by 861 · see citing works
Self-citationEmbodied Perception and the Economy of Action
Proffitt, D. R. (2006) · Perspectives on Psychological Science · doi:10.1111/j.1745-6916.2006.00008.x · Cited by 696 · see citing works
Effects of light on human circadian rhythms, sleep and mood
Blume, C., Garbazza, C., & Spitschan, M. (2019) · Somnologie · doi:10.1007/s11818-019-00215-x · Cited by 695 · see citing works
Cajochen, C., Zeitzer, J. M., Czeisler, C. A., & Dijk, D.-J. (2000) · Behavioural Brain Research · doi:10.1016/s0166-4328(00)00236-9 · Cited by 653 · see citing works
Viola, A. U., James, L. M., Schlangen, L. J., & Dijk, D.-J. (2008) · Scandinavian Journal of Work, Environment & Health · doi:10.5271/sjweh.1268 · Cited by 565 · see citing works
A neural mechanism for exacerbation of headache by light
Noseda, R., Kainz, V., Jakubowski, M., Gooley, J. J., Saper, C. B., Digre, K., & Burstein, R. (2010) · Nature Neuroscience · doi:10.1038/nn.2475 · Cited by 565 · see citing works
Chellappa, S. L., Steiner, R., Blattner, P., Oelhafen, P., Götz, T., & Cajochen, C. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016429 · Cited by 546 · see citing works
Light as a modulator of cognitive brain function.
Vandewalle, G., Maquet, P., & Dijk, D.-J. (2009) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2009.07.004 · Cited by 556 · see citing works
Strange vision: ganglion cells as circadian photoreceptors
Berson, D. (2003) · Trends in Neurosciences · doi:10.1016/s0166-2236(03)00130-9 · Cited by 546 · see citing works
White Collar-1, a Circadian Blue Light Photoreceptor, Binding to the <i>frequency</i> Promoter
Froehlich, A. C., Liu, Y., Loros, J. J., & Dunlap, J. C. (2002) · Science · doi:10.1126/science.1073681 · Cited by 520 · see citing works
Light Affects Mood and Learning through Distinct Retina-Brain Pathways
Fernandez, D. C., Fogerson, P. M., Lazzerini Ospri, L., Thomsen, M. B., Layne, R. M., Severin, D., Zhan, J., Singer, J. H., Kirkwood, A., Zhao, H., et al. (2018) · Cell · doi:10.1016/j.cell.2018.08.004 · Cited by 505 · see citing works
Effects of blue light on the circadian system and eye physiology
Tosini, G., Ferguson, I., & Tsubota, K. (2016) · Molecular Vision · doi:10.63500/mv_v22_61 · Cited by 517 · see citing works
Gooley, J. J., Rajaratnam, S. M. W., Brainard, G. C., Kronauer, R. E., Czeisler, C. A., & Lockley, S. W. (2010) · Science Translational Medicine · doi:10.1126/scitranslmed.3000741 · Cited by 447 · see citing works
LEDs for photons, physiology and food
Pattison, P. M., Tsao, J. Y., Brainard, G. C., & Bugbee, B. (2018) · Nature · doi:10.1038/s41586-018-0706-x · Cited by 410 · see citing works
Circadian photoreception: ageing and the eye's important role in systemic health
Turner, P. L., & Mainster, M. A. (2008) · British Journal of Ophthalmology · doi:10.1136/bjo.2008.141747 · Cited by 315 · see citing works
The inner clock-Blue light sets the human rhythm
Wahl, S., Engelhardt, M., Schaupp, P., Lappe, C., & Ivanov, I. V. (2019) · Journal of Biophotonics · doi:10.1002/jbio.201900102 · Cited by 293 · see citing works
Acute alerting effects of light: A systematic literature review
Souman, J. L., Tinga, A. M., te Pas, S. F., van Ee, R., & Vlaskamp, B. N. S. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.09.016 · Cited by 293 · see citing works
Chemistry and Biology of Vision
Palczewski, K. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.r111.301150 · Cited by 289 · see citing works
Vandewalle, G., Gais, S., Schabus, M., Balteau, E., Carrier, J., Darsaud, A., Sterpenich, V., Albouy, G., Dijk, D. J., & Maquet, P. (2007) · Cerebral Cortex · doi:10.1093/cercor/bhm007 · Cited by 277 · see citing works
Sensitivity of the Human Circadian System to Short-Wavelength (420-nm) Light
Brainard, G. C., Sliney, D., Hanifin, J. P., Glickman, G., Byrne, B., Greeson, J. M., Jasser, S., Gerner, E., & Rollag, M. D. (2008) · Journal of Biological Rhythms · doi:10.1177/0748730408323089 · Cited by 260 · see citing works
Self-citationLight and the laboratory mouse
Peirson, S. N., Brown, L. A., Pothecary, C. A., Benson, L. A., & Fisk, A. S. (2018) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2017.04.007 · Cited by 234 · see citing works
“Projections from melanopsin pRGCs to the olivary pretectal nucleus (OPN) mediate pupillary light responses, whereas projections to the ventrolateral preoptic nuclei (VLPO) modulate sleep.”
InfluentialSpectral quality of light modulates emotional brain responses in humans.
Vandewalle, G., Schwartz, S., Grandjean, D., Wuillaume, C., Balteau, E., Degueldre, C., Schabus, M., Phillips, C., Luxen, A., Dijk, D. J., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010180107 · Cited by 255 · see citing works
Circadian rhythms, refractive development, and myopia
Chakraborty, R., Ostrin, L. A., Nickla, D. L., Iuvone, P. M., Pardue, M. T., & Stone, R. A. (2018) · Ophthalmic and Physiological Optics · doi:10.1111/opo.12453 · Cited by 235 · see citing works
Effects of circadian disruption on the cardiometabolic system
Rüger, M., & Scheer, F. A. J. L. (2009) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-009-9122-8 · Cited by 232 · see citing works
Santhi, N., Thorne, H. C., van der Veen, D. R., Johnsen, S., Mills, S. L., Hommes, V., Schlangen, L. J. M., Archer, S. N., & Dijk, D. (2012) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2011.00970.x · Cited by 219 · see citing works
Münch, M., Kobialka, S., Steiner, R., Oelhafen, P., Wirz-Justice, A., & Cajochen, C. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00478.2005 · Cited by 202 · see citing works
Neuropsin (Opn5): a novel opsin identified in mammalian neural tissue<sup>1</sup>
Tarttelin, E. E., Bellingham, J., Hankins, M. W., Foster, R. G., & Lucas, R. J. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)01212-2 · Cited by 198 · see citing works
Lucas, R. J., Lall, G. S., Allen, A. E., & Brown, T. M. (2012) · Progress in brain research · doi:10.1016/b978-0-444-59427-3.00001-0 · Cited by 195 · see citing works
Opponent melanopsin and S-cone signals in the human pupillary light response
Spitschan, M., Jain, S., Brainard, D. H., & Aguirre, G. K. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1400942111 · Cited by 192 · see citing works
Arendt, D., Tessmar, K., de Campos-Baptista, M.-I. M., Dorresteijn, A., & Wittbrodt, J. (2002) · Development · doi:10.1242/dev.129.5.1143 · Cited by 192 · see citing works
Selby, C. P., Thompson, C., Schmitz, T. M., Van Gelder, R. N., & Sancar, A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.260498597 · Cited by 184 · see citing works
Daily and seasonal variation in the spectral composition of light exposure in humans
Thorne, H. C., Jones, K. H., Peters, S. P., Archer, S. N., & Dijk, D.-J. (2009) · Chronobiology International · doi:10.1080/07420520903044315 · Cited by 153 · see citing works
Intrinsically photosensitive retinal ganglion cells of the human retina
Mure, L. S. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.636330 · Cited by 151 · see citing works
The chronobiology and neurobiology of winter seasonal affective disorder
Levitan, R. D. (2007) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2007.9.3/rlevitan · Cited by 149 · see citing works
Melanopsin contributions to non-visual and visual function
Spitschan, M. (2019) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2019.06.004 · Cited by 146 · see citing works
Evening exposure to blue light stimulates the expression of the clock gene <i>PER2</i> in humans
Cajochen, C., Jud, C., Münch, M., Kobialka, S., Wirz‐Justice, A., & Albrecht, U. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04613.x · Cited by 144 · see citing works
Age-Related Changes in Acute and Phase-Advancing Responses to Monochromatic Light
Sletten, T. L., Revell, V. L., Middleton, B., Lederle, K. A., & Skene, D. J. (2009) · Journal of Biological Rhythms · doi:10.1177/0748730408328973 · Cited by 137 · see citing works
The Coevolution of Blue-Light Photoreception and Circadian Rhythms
Gehring, W., & Rosbash, M. (2003) · Journal of Molecular Evolution · doi:10.1007/s00239-003-0038-8 · Cited by 132 · see citing works
Lipids around the Clock: Focus on Circadian Rhythms and Lipid Metabolism
Gnocchi, D., Pedrelli, M., Hurt-Camejo, E., & Parini, P. (2015) · Biology · doi:10.3390/biology4010104 · Cited by 115 · see citing works
Phase advancing the human circadian clock with blue-enriched polychromatic light
Smith, M. R., Revell, V. L., & Eastman, C. I. (2009) · Sleep Medicine · doi:10.1016/j.sleep.2008.05.005 · Cited by 114 · see citing works
Neuroprotection in Glaucoma: Animal Models and Clinical Trials
Almasieh, M., & Levin, L. A. (2017) · Annual Review of Vision Science · doi:10.1146/annurev-vision-102016-061422 · Cited by 111 · see citing works
Vertebrate ancient opsin and melanopsin: divergent irradiance detectors
Davies, W. L., Hankins, M. W., & Foster, R. G. (2010) · Photochemical & Photobiological Sciences · doi:10.1039/c0pp00203h · Cited by 100 · see citing works
Temporal integration of light flashes by the human circadian system
Najjar, R. P., & Zeitzer, J. M. (2016) · Journal of Clinical Investigation · doi:10.1172/jci82306 · Cited by 99 · see citing works
Phase Delaying the Human Circadian Clock with Blue-Enriched Polychromatic Light
Smith, M. R., & Eastman, C. I. (2009) · Chronobiology International · doi:10.1080/07420520902927742 · Cited by 100 · see citing works
Meesters, Y., Dekker, V., Schlangen, L. J., Bos, E. H., & Ruiter, M. J. (2011) · BMC Psychiatry · doi:10.1186/1471-244x-11-17 · Cited by 98 · see citing works
“A recent scientific development has been the discovery of a novel photoreceptor, melanopsin, within the basal ganglia of the retina [4-6].”
BackgroundRetina, retinol, retinal and the natural history of vitamin A as a light sensor
Zhong, M., Kawaguchi, R., Kassai, M., & Sun, H. (2012) · Nutrients · doi:10.3390/nu4122069 · Cited by 89 · see citing works
Melanopsin-expressing retinal ganglion cells: implications for human diseases
La Morgia, C., Ross-Cisneros, F. N., Hannibal, J., Montagna, P., Sadun, A. A., & Carelli, V. (2011) · Vision Research · doi:10.1016/j.visres.2010.07.023 · Cited by 84 · see citing works
Retinal Ganglion Cell Types and Their Central Projections
Berson, D. M. (2008) · The Senses: A Comprehensive Reference · doi:10.1016/b978-012370880-9.00280-2 · Cited by 82 · see citing works
Wahnschaffe, A., Haedel, S., Rodenbeck, A., Stoll, C., Rudolph, H., Kozakov, R., Schoepp, H., & Kunz, D. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14022573 · Cited by 76 · see citing works
Höhn, C., Schmid, S. R., Plamberger, C. P., Bothe, K., Angerer, M., Gruber, G., Pletzer, B., & Hoedlmoser, K. (2021) · Clocks & Sleep · doi:10.3390/clockssleep3010005 · Cited by 61 · see citing works
“, rods and cones) but also by specific intrinsically photosensitive retinal ganglion cells (ipRGCs) [15], which contain the photopigment melanopsin [16,17].”
BackgroundBrzezinski, J. A., Brown, N. L., Tanikawa, A., Bush, R. A., Sieving, P. A., Vitaterna, M. H., Takahashi, J. S., & Glaser, T. (2005) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.04-1123 · Cited by 60 · see citing works
Revell, V. L., Barrett, D. C. G., Schlangen, L. J. M., & Skene, D. J. (2010) · Chronobiology International · doi:10.3109/07420528.2010.516048 · Cited by 57 · see citing works
Campbell, I., Sharifpour, R., & Vandewalle, G. (2023) · Clocks & Sleep · doi:10.3390/clockssleep5010012 · Cited by 43 · see citing works
Processing of daily and seasonal light information in the mammalian circadian clock.
Meijer, J. H., Michel, S., & Vansteensel, M. J. (2007) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2007.01.018 · Cited by 40 · see citing works
Impact of age on human non-visual responses to light
REVELL, V. L., & SKENE, D. J. (2010) · Sleep and Biological Rhythms · doi:10.1111/j.1479-8425.2009.00418.x · Cited by 31 · see citing works
Bonmati-Carrion, M. A., Baño-Otalora, B., Madrid, J. A., & Rol, M. A. (2017) · Scientific Reports · doi:10.1038/s41598-017-08691-7 · Cited by 26 · see citing works
Direct visual and circadian pathways target neuroendocrine cells in primates
Abizaid, A., Horvath, B., Keefe, D. L., Leranth, C., & Horvath, T. L. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03737.x · Cited by 22 · see citing works
Wang, C., Su, K., Hu, L., Wu, S., Zhan, Y., Yang, C., & Xiang, J. (2024) · Indoor Environments · doi:10.1016/j.indenv.2024.100015 · Cited by 2 · see citing works
- Authors
- Provencio, I., Rodriguez, I. R., Jiang, G., Hayes, W. P., Moreira, E. F., & Rollag, M. D.
- Affiliations
- Uniformed Services University of the Health Sciences (US)
- Catholic University of America (US)
- National Institutes of Health (US)
- ORCID
- Provencio, Ignacio
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2000-01-15
- Volume
- 20
- Issue
- 2
- Pages
- 600-605
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6772411
- OpenAlex
- W2151131721
- Cited by
- 1,290
- References
- 2
- Citations by year
- 2026: 30 · 2025: 53 · 2024: 61 · 2023: 58 · 2022: 61 · 2021: 69 · 2020: 49 · 2019: 67 · 2018: 52 · 2017: 65 · 2016: 68 · 2015: 49 · 2014: 59 · 2013: 40 · 2012: 51
- FWCI
- 16.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (9809916)
- Uniformed Services University of the Health Sciences
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
- Keywords
- melanopsin, opsin, inner retina, ganglion cells, amacrine cells, gene structure, non-visual photoreception, circadian rhythm, melatonin suppression, suprachiasmatic nucleus, retinal gene expression
- MeSH terms
- Melanopsin, Amino Acid Sequence, Animals, Chromosome Mapping, Chromosomes, Human, Pair 10, Cloning, Molecular, Exons, Humans, Macaca mulatta, Molecular Sequence Data, Organ Specificity, Primates, Retina, Retinal Ganglion Cells, Sequence Alignment, Rod Opsins, Sequence Homology, Amino Acid, In Situ Hybridization, Mice
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