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cycles and free-ran under constant darkness in a way expected from the normal mice. Researchers in
Provencio's lab thus concluded that melanopsin was not involved in the functioning of the master clock oscillation. On the other hand, Opn4-/- mice had difficulties adjusting to new phases in response to pulses of monochromatic light. The implication was that melanopsin was necessary for phase resetting but other mechanisms of light inputs might be involved in circadian entrainment as well.
182:. This resulted in lowered responsiveness to light/dark cycles; a similar characteristic was observed in gene-knockout mutants lacking rods, cones or melanopsin. Furthermore, light-induced negative masking, mediated by rods, cones and/or melanopsin cells, was missing in the mice lacking melanopsin cells. Therefore, Provencio suggested that cells containing melanopsin might be required to transmit rod and/or cone information for certain non-image forming visual responses.
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behavior. From these results, Provencio concluded that RPE65 is not necessary for the function of ipRGCs. However, because of the interesting restoration of circadian photosensitivity in rodless, RPE-less mice, there seems to be a mechanism by which rods can influences ipRGCs and rods may interact.
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To further investigate the role of melanopsin in light-induced phase shifting in mammals, the
Provencio lab studied the locomotor activities of melanopsin-null mice (Opn4 -/-) in response to light. The Opn4 -/- mice showed similar circadian behaviors as the normal mice: they entrained to light/dark
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of blind patients and babies was a common practice for cosmetic or analgesic reasons, doctors now must make a more cautious decision on whether to enucleate blind patients, especially infants, because they may still have functioning photosensitive retinal ganglion cells that express melanopsin. In
220:
Provencio's research team has found that in albino mice, the amount of melanopsin protein in various retinal cells varies based on the environmental light conditions. In constant light conditions, melanopsin cell number did not increase. However, when these constant-light mice were exposed to
198:
that express melanopsin have also been found in humans, these studies suggest that blind humans who still retain functional melanopsin cells are those who are able to entrain to daily light cycles. These studies also show that blind patients who cannot entrain and lack melanopsin cells have a
158:
but with functional rods and cones were also able to entrain. However, when melanopsin was knocked out in blind mice without rods and cones, they exhibited “complete loss of photoentrainment of the circadian oscillator, pupillary light responses, photic suppression of
98:, Provencio held assistant and associate professorships at Uniformed Services University, Department of Anatomy, Physiology, and Genetics where he still maintains an adjunct associate professorship. Provencio is a full professor at the University of Virginia.
135:, where it is only present in the eye. The unique inner retinal localization of melanopsin indicated that melanopsin was not involved in image formation. Later, he demonstrated that the melanopsin pigment might be involved in
163:) are sufficient to induce a response to light. However, in the absence of either rods and cones or melanopsin, melanopsin becomes necessary for photoentrainment of the circadian oscillator and for other photic responses.
159:
arylalkylamine-N-acetyltransferase transcript, and acute suppression of locomotor activity by light.” Provencio concluded that either melanopsin-containing retinal ganglion cells or outer-retinal photoreceptors (
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light-dark schedules, there was regain of melanopsin cell number. This study shows that bouts of darkness or the order of light and dark periods may control the normal development of the melanopsin system.
568:
Panda, S.; Provencio, I; Tu, DC; Pires, SS; Rollag, MD; Castrucci, AM; Pletcher, MT; Sato, TK; et al. (2003). "Melanopsin is
Required for Non-Image-Forming Photic Responses in Blind Mice".
405:
628:
Panda, S.; Sato, TK; Castrucci, AM; Rollag, MD; Degrip, WJ; Hogenesch, JB; Provencio, I; Kay, SA (2002). "Melanopsin (Opn4) Requirement for Normal Light-Induced
Circadian Phase Shifting".
240:
in rods and cones. RPE65 knockout mice (Rpe65(-/-)) showed much weaker phase shifts when compared to rodless, coneless mice, which suggested that RPE65 might have other roles.
70:, Provencio became interested in neuroscience while studying crayfish, cockroaches, and fireflies under Jon Copeland. From 1987 to 1989 he worked as a lab technician in
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Czeisler, Charles A.; Shanahan, Theresa L.; Klerman, Elizabeth B.; Martens, Heinz; Brotman, Daniel J.; Emens, Jonathan S.; Klein, Torsten; Rizzo, Joseph F. (1995).
243:
To further define the functions of RPE65, Provencio took Rpe65(-/-) mice and also eliminated rods. The technique used for this was insertion of the rdta
43:
409:
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686:"Targeted Destruction of Photosensitive Retinal Ganglion Cells with a Saporin Conjugate Alters the Effects of Light on Mouse Circadian Rhythms"
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and its function in photoentrainment supports earlier studies showing that some blind patients can entrain to a daily light cycle. Since
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Göz, Didem; Studholme, Keith; Lappi, Douglas A.; Rollag, Mark D.; Provencio, Ignacio; Morin, Lawrence P. (2008). Greene, Ernest (ed.).
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knockout mice (Opn4(-/-)). This created double RPE and melanopsin knockout mice, which resulted in abnormal photoentrainment and
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75:
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In 2008, the
Provencio lab was able to specifically destroy melanopsin cells in the fully developed mouse retina using an
95:
59:
35:
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for those with circadian rhythm sleep disorders that specifically try to stimulate melanopsin cells in blind patients.
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returned in these mice without RPE65 protein and without rods, versus mice without RPE65 protein that still had rods.
136:
887:"Postnatal Development and Functional Adaptations of the Melanopsin Photoreceptive System in the Albino Mouse Retina"
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366:
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941:"Nonvisual light responses in the Rpe65 knockout mouse: Rod loss restores sensitivity to the melanopsin system"
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Gooley, J. J.; Rajaratnam, S. M. W.; Brainard, G. C.; Kronauer, R. E.; Czeisler, C. A.; Lockley, S. W. (2010).
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831:"Spectral Responses of the Human Circadian System Depend on the Irradiance and Duration of Exposure to Light"
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Gonzalez-Menendez, I.; Contreras, F.; Cernuda-Cernuda, R.; Provencio, I.; Garcia-Fernandez, J. M. (2010).
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Provencio, Ignacio; Jiang, Guisen; De Grip, Willem J.; Hayes, William Pär; Rollag, Mark D. (1998).
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232:. RPE65 is an important protein found in intrinsically photosensitive retinal ganglion cells (
82:. He graduated in 1987 from Swarthmore College with a B.A. in Biology and went on to earn his
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Provencio, I; Rodriguez, IR; Jiang, G; Hayes, WP; Moreira, EF; Rollag, MD (2000).
90:, a university with a strong network of circadian biologists, in 1996. During his
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Doyle, S. E.; Castrucci, A. M.; McCall, M.; Provencio, I.; Menaker, M. (2006).
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154:) still had eye-mediated responses to light. Mice with the melanopsin gene
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785:"Circadian Rhythm Sleep Disorder (formerly Sleep-Wake Schedule Disorder)"
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408:. University of Virginia, Department of Ophthalmology. Archived from
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Provencio, I; Jiang, G; De Grip, WJ; Hayes, WP; Rollag, MD (1998).
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He found that blind mice without classical photoreceptor cells (
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369:. Society for Research on Biological Rhythms. Archived from
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In a 2006 study, Provencio explored the role of the protein
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Provencio also took Rpe65(-/-) mice and crossed them with
247:, which selectively kills rods. They found that circadian
42:. Provencio served as the program committee chair of the
123:. In 2000, he showed that melanopsin is also present in
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addition, there are now studies attempting to optimize
455:"Melanopsin: An opsin in melanophores, brain, and eye"
309:"Melanopsin: an opsin in melanophores, brain, and eye"
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891:Investigative Ophthalmology & Visual Science
367:"The Society for Research on Biological Rhythms"
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236:) that is necessary for regeneration of visual
119:in the photosensitive skin melanophores of the
1029:The Society for Research on Biological Rhythms
199:significantly greater risk of suffering from
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1034:Search Results for author Provencio I
78:, where he was introduced to the field of
44:Society for Research on Biological Rhythms
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107:Role of melanopsin in photic responses
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406:"UVA Vision Research Group Directory"
66:. During his undergraduate career at
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22:(born 29 June 1965) is an American
531:10.1523/jneurosci.20-02-00600.2000
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808:"Non-24-hour sleep-wake syndrome"
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201:circadian rhythm sleep disorders
749:New England Journal of Medicine
1054:University of Virginia faculty
835:Science Translational Medicine
391:Scientific American May 2011.
111:In 1998, Provencio discovered
76:Massachusetts General Hospital
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186:Entrainment in blind patients
96:Uniformed Services University
36:photosensitive ganglion cells
847:10.1126/scitranslmed.3000741
711:10.1371/journal.pone.0003153
143:to light cycles in mammals.
60:Lebanon Catholic High School
762:10.1056/NEJM199501053320102
518:The Journal of Neuroscience
174:made of an anti-melanopsin
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787:. Armenian Medical Network
459:Proc. Natl. Acad. Sci. USA
178:conjugated to the protein
74:'s research laboratory at
190:Provencio's discovery of
434:. University of Virginia
958:10.1073/pnas.0600934103
650:10.1126/science.1076848
590:10.1126/science.1086179
58:, Germany and attended
16:American neuroscientist
283:University of Virginia
196:retinal ganglion cells
88:University of Virginia
54:Provencio was born in
26:and the discoverer of
480:10.1073/pnas.95.1.340
334:10.1073/pnas.95.1.340
34:found in specialized
903:10.1167/iovs.10-5253
404:Provencio, Ignacio.
141:circadian oscillator
951:(27): 10432–10437.
810:. Medlink Neurology
702:2008PLoSO...3.3153G
642:2002Sci...298.2213P
582:2003Sci...301..525P
471:1998PNAS...95..340P
432:"Ignacio Provencio"
325:1998PNAS...95..340P
121:African clawed frog
46:from 2008 to 2010.
68:Swarthmore College
1023:Ignacio Provencio
1012:Ignacio Provencio
806:Baruch El-Ad MD.
394:. April 20, 2011.
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238:chromophore
205:enucleation
172:immunotoxin
156:knocked out
137:entrainment
64:Lebanon, PA
1048:Categories
294:References
273:Melanopsin
256:melanopsin
192:melanopsin
113:melanopsin
28:melanopsin
814:April 19,
791:April 19,
245:transgene
115:as a new
86:from the
50:Biography
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690:PLOS ONE
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267:See also
203:. While
176:antibody
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1002:Scholia
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698:Bibcode
638:Bibcode
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570:Science
541:6772411
499:9419377
467:Bibcode
416:9 April
377:9 April
353:9419377
321:Bibcode
260:diurnal
180:saporin
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