Melanopsin is required for non-image-forming photic responses in blind mice
Abstract
Although mice lacking rod and cone photoreceptors are blind, they retain many eye-mediated responses to light, possibly through photosensitive retinal ganglion cells. These cells express melanopsin, a photopigment that confers this photosensitivity. Mice lacking melanopsin still retain nonvisual photoreception, suggesting that rods and cones could operate in this capacity. We observed that mice with both outer-retinal degeneration and a deficiency in melanopsin exhibited complete loss of photoentrainment of the circadian oscillator, pupillary light responses, photic suppression of arylalkylamine-N-acetyltransferase transcript, and acute suppression of locomotor activity by light. This indicates the importance of both nonvisual and classical visual photoreceptor systems for nonvisual photic responses in mammals.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Melanopsin (λmax ~480 nm) is expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs) that mediate circadian entrainment, the pupillary light reflex, and light-regulated changes in mood.
“Additionally, melanopsin (λmax ~480 nm) is expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs) that mediate circadian entrainment, the pupillary light reflex, and light-regulated changes in mood (Panda et al., 2003; Hattar et al., 2003; Fernandez et al., 2018).”
From Ventral striatum dopamine release encodes unique properties of visual stimuli in mice (2023) · cites this paper as Panda et al., 2003
Cites
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
Hattar, S., Liao, H.-W., Takao, M., Berson, D. M., & Yau, K.-W. (2002) · Science · doi:10.1126/science.1069609 · Cited by 2,734 · see citing works
Emery, P., So, W. V., Kaneko, M., Hall, J. C., & Rosbash, M. (1998) · Cell · doi:10.1016/s0092-8674(00)81637-2 · Cited by 912 · 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-citationDiminished Pupillary Light Reflex at High Irradiances in Melanopsin-Knockout Mice
Lucas, R. J., Hattar, S. S., Takao, M., Berson, D. M., Foster, F., & Yau, K. (2003) · Science · doi:10.1126/science.1077293 · Cited by 835 · see citing works
Phytochromes and Cryptochromes in the Entrainment of the Arabidopsis Circadian Clock
Somers, D. E., Devlin, P. F., & Kay, S. A. (1998) · Science · doi:10.1126/science.282.5393.1488 · Cited by 788 · see citing works
Self-citationRole of Melanopsin in Circadian Responses to Light
Ruby, N. F., Brennan, T. J., Xie, X., Cao, V. H., Franken, P., Heller, H. C., & O’Hara, B. F. (2002) · Science · doi:10.1126/science.1076701 · Cited by 647 · see citing works
Characterization of an ocular photopigment capable of driving pupillary constriction in mice
Lucas, R. J., Douglas, R. H., & Foster, R. G. (2001) · Nature Neuroscience · doi:10.1038/88443 · Cited by 614 · see citing works
Regulation of the Mammalian Pineal by Non-rod, Non-cone, Ocular Photoreceptors
Lucas, R. J., Freedman, M. S., Muñoz, M., García-Fernández, J. M., & Foster, F. (1999) · Science · doi:10.1126/science.284.5413.505 · Cited by 525 · see citing works
Circadian photoreception in the retinally degenerate mouse (rd/rd)
Foster, F., Provencio, I., Hudson, D. M., Fiske, S., DeGrip, W. J., & Menaker, M. (1991) · Journal of Comparative Physiology A · doi:10.1007/bf00198171 · Cited by 510 · see citing works
Self-citationMiyamoto, Y., & Sancar, A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6097 · Cited by 406 · see citing works
The Circadian Clock of Fruit Flies Is Blind after Elimination of All Known Photoreceptors
Helfrich‐Förster, C., Winter, C., Hofbauer, A., Hall, J. C., & Stanewsky, R. (2001) · Neuron · doi:10.1016/s0896-6273(01)00277-x · Cited by 379 · see citing works
Rapid Light-Induced Decrease in Pineal Serotonin N -Acetyltransferase Activity
Klein, D. C., & Weller, J. L. (1972) · Science · doi:10.1126/science.177.4048.532 · Cited by 358 · see citing works
Roseboom, P. H., Coon, S. L., Baler, R., et al. (1996) · Endocrinology · doi:10.1210/endo.137.7.8770929 · Cited by 317 · see citing works
Melanopsin retinal ganglion cells receive bipolar and amacrine cell synapses
Belenky, M. A., Smeraski, C. A., Provencio, I., Sollars, P. J., & Pickard, G. E. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10652 · Cited by 284 · see citing works
Self-citationNon-rod, non-cone photoreception in the vertebrates
Foster, F., & Hankins, M. W. (2002) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(02)00036-8 · Cited by 191 · see citing works
Absence of extraocular photoreception in diurnal and nocturnal rodents exposed to direct sunlight
Nelson, R. J., & Zucker, I. (1981) · Comparative Biochemistry and Physiology Part A Physiology · doi:10.1016/0300-9629(81)90651-4 · Cited by 166 · see citing works
Devlin, P. F., & Kay, S. A. (2001) · Annual Review of Physiology · doi:10.1146/annurev.physiol.63.1.677 · Cited by 160 · see citing works
Self-citationReduced Pupillary Light Responses in Mice Lacking Cryptochromes
Gelder, R. N. V., Wee, R., Lee, J. A., & Tu, D. C. (2003) · Science · doi:10.1126/science.1079536 · Cited by 110 · see citing works
Self-citationLoss of Photic Entrainment and Altered Free-Running Circadian Rhythms inmath5−/−Mice
Wee, R., Castrucci, A. M. D. L., Provencio, I., Gan, L., & Gelder, R. N. V. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-23-10427.2002 · Cited by 57 · see citing works
Self-citationGelder, R. N. V., Gibler, T. M., Tu, D. C., EMBRY, K., Selby, C. P., Thompson, C. L., & Sancar, A. (2002) · Journal of Neurogenetics · doi:10.1080/01677060215306 · Cited by 30 · see citing works
Self-citationAbsence of light-dark entrainment on the sleep-waking cycle in mice with intact visual perception
Faradji, H., Cespuglio, R., Rondot, G., et al. (1980) · Brain Research · doi:10.1016/s0006-8993(80)80033-3 · Cited by 16 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Circadian physiology of metabolism
Panda, S. (2016) · Science · doi:10.1126/science.aah4967 · Cited by 1,092 · see citing works
Self-citationCentral 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
Mammalian circadian biology: elucidating genome-wide levels of temporal organization
Lowrey, P. L., & Takahashi, J. S. (2004) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev.genom.5.061903.175925 · Cited by 976 · 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
Modulation of locomotor activity in larval zebrafish during light adaptation
Burgess, H. A., & Granato, M. (2007) · Journal of Experimental Biology · doi:10.1242/jeb.003939 · Cited by 525 · 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
Circadian clocks: regulators of endocrine and metabolic rhythms
Hastings, M., O’Neill, J. S., & Maywood, E. S. (2007) · Journal of Endocrinology · doi:10.1677/joe-07-0378 · Cited by 426 · see citing works
Sleep and Circadian Rhythms in Humans
Czeisler, C. A., & Gooley, J. J. (2007) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.2007.72.064 · Cited by 425 · see citing works
Circadian system, sleep and endocrinology
Morris, C. J., Aeschbach, D., & Scheer, F. A. J. L. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.09.003 · Cited by 403 · see citing works
Batten, M. L., Imanishi, Y., Maeda, T., Tu, D. C., Moise, A. R., Bronson, D., Possin, D., Van Gelder, R. N., Baehr, W., & Palczewski, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312410200 · Cited by 368 · see citing works
Self-citationRestoration of visual function in retinal degeneration mice by ectopic expression of melanopsin
Lin, B., Koizumi, A., Tanaka, N., Panda, S., & Masland, R. H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806114105 · Cited by 302 · see citing works
Self-citationInterconnection between circadian clocks and thyroid function
Ikegami, K., Refetoff, S., Van Cauter, E., & Yoshimura, T. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0237-z · Cited by 251 · 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
Meléndez-Fernández, O. H., Liu, J. A., & Nelson, R. J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043392 · Cited by 227 · see citing works
Gronfier, C., Wright, K. P., Kronauer, R. E., Jewett, M. E., & Czeisler, C. A. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00385.2003 · Cited by 212 · 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
Artificial light at night: melatonin as a mediator between the environment and epigenome
Haim, A., & Zubidat, A. E. (2015) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2014.0121 · Cited by 133 · see citing works
Mammalian circadian systems: Organization and modern life challenges
Finger, A., & Kramer, A. (2021) · Acta Physiologica · doi:10.1111/apha.13548 · Cited by 117 · see citing works
Retinoids and Retinal Diseases
Kiser, P. D., & Palczewski, K. (2016) · Annual Review of Vision Science · doi:10.1146/annurev-vision-111815-114407 · Cited by 108 · see citing works
Photic Entrainment of the Circadian System
Ashton, A., Foster, R., & Jagannath, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020729 · Cited by 106 · 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
Vicente-Tejedor, J., Marchena, M., Ramírez, L., García-Ayuso, D., Gómez-Vicente, V., Sánchez-Ramos, C., de la Villa, P., & Germain, F. (2018) · PLOS ONE · doi:10.1371/journal.pone.0194218 · Cited by 90 · see citing works
Retina, 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
Lhx1 maintains synchrony among circadian oscillator neurons of the SCN
Hatori, M., Gill, S., Mure, L. S., Goulding, M., O'Leary, D. D. M., & Panda, S. (2014) · eLife · doi:10.7554/elife.03357 · Cited by 81 · see citing works
Self-citationVisual responses in mice lacking critical components of all known retinal phototransduction cascades
Allen, A. E., Cameron, M. A., Brown, T. M., Vugler, A. A., & Lucas, R. J. (2010) · PLoS ONE · doi:10.1371/journal.pone.0015063 · Cited by 64 · see citing works
Strong resetting of the mammalian clock by constant light followed by constant darkness
Chen, R., Seo, D.-O., Bell, E., von Gall, C., & Lee, C. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.2191-08.2008 · Cited by 53 · see citing works
In synch but not in step: Circadian clock circuits regulating plasticity in daily rhythms
Evans, J. A., & Gorman, M. R. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2016.01.072 · Cited by 49 · 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
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
Ventral striatum dopamine release encodes unique properties of visual stimuli in mice
Gonzalez, L. S., Fisher, A. A., D'Souza, S. P., Cotella, E. M., Lang, R. A., & Robinson, J. E. (2023) · eLife · doi:10.7554/elife.85064 · Cited by 18 · see citing works
Anatomy of the Mammalian Circadian System
Gooley, J. J., & Saper, C. B. (2017) · Principles and Practice of Sleep Medicine · doi:10.1016/b978-0-323-24288-2.00033-7 · Cited by 9 · see citing works
Short wavelength light administered just prior to waking: a pilot study
Grandner, M. A., Kripke, D. F., Elliott, J., & Cole, R. (2013) · Biological Rhythm Research · doi:10.1080/09291016.2011.632578 · Cited by 9 · see citing works
“More recently, melanopsin-producing retinal ganglion cells were discovered to be the primary mechanism through which environmental light is encoded as circadian information (Bellingham and Foster 2002; Hannibal 2002; Hattar et al. 2002; Panda et al. 2003).”
Background
- Authors
- Panda, S., Provencio, I., Tu, D. C., Pires, S. S., Rollag, M. D., Castrucci, A. M., Pletcher, M. T., Sato, T. K., Wiltshire, T., Andahazy, M., Kay, S. A., Van Gelder, R. N., & Hogenesch, J. B.
- Affiliations
- Scripps Research Institute (US)
- Genomics Institute of the Novartis Research Foundation, 10675 John J. Hopkins Drive, San Diego, CA 92121, USA. Department of Cell Biology, Department of Neuropharmacology, Scripps Research Institute, 10550 North Torrey Pines Road, San Diego, CA 92037, USA. Department of Anatomy, Physiology, and Genetics, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. Department of Ophthalmology and Visual Sciences, Department of Molecular Biology and Pharmacology, Washington...
- Corresponding author
- Panda, Satchidananda
- Provencio, Ignacio
- Tu, Daniel C.
- Hogenesch, John B.
- ORCID
- Venue
- Science
- Published
- 2003-07-25
- Volume
- 301
- Issue
- 5632
- Pages
- 525-527
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2105050095
- Cited by
- 711
- References
- 22
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 15 · 2023: 23 · 2022: 23 · 2021: 24 · 2020: 26 · 2019: 36 · 2018: 35 · 2017: 42 · 2016: 46 · 2015: 29 · 2014: 40 · 2013: 31 · 2012: 26
- FWCI
- 16.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1k08ey000403-01)
- National Institute of Mental Health (MH 62405, MH-51573, R01MH062405, R01MH051573)
- National Eye Institute (R01 EY14988, R01EY014988, K08 EY 00403)
- 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 › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- melanopsin, non-visual photoreception, blind mice, rod and cone photoreceptors, retinal ganglion cells, circadian photoentrainment, pupillary light reflex, arylalkylamine N-acetyltransferase, outer retinal degeneration, phototransduction
- MeSH terms
- Melanopsin, Animals, Arylamine N-Acetyltransferase, Blindness, Circadian Rhythm, Light, Mice, Inbred C3H, Motor Activity, Reflex, Pupillary, Retinal Degeneration, Retinal Ganglion Cells, Suprachiasmatic Nucleus, Signal Transduction, Rod Opsins, Photoreceptor Cells, Vertebrate, Mice, Light Signal Transduction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
