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      THE INJURY RESISTANT ABILITY OF MELANOPSIN-EXPRESSING INTRINSICALLY PHOTOSENSITIVE RETINAL GANGLION CELLS

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          Abstract

          Neurons in the mammalian retina expressing the photopigment melanopsin have been identified as a class of intrinsically photosensitive retinal ganglion cells (ipRGCs). This discovery more than a decade ago has opened up an exciting new field of retinal research, and following the initial identification of photosensitive ganglion cells, several subtypes have been described. A number of studies have shown that ipRGCs subserve photoentrainment of circadian rhythms. They also influence other non-image forming functions of the visual system, such as the pupillary light reflex, sleep, cognition, mood, light aversion and development of the retina. These novel photosensitive neurons also influence form vision by contributing to contrast detection. Furthermore, studies have shown that ipRGCs are more injury-resistant following optic nerve injury, in animal models of glaucoma, and in patients with mitochondrial optic neuropathies, i.e., Leber’s hereditary optic neuropathy and dominant optic atrophy. There is also an indication that these cells may be resistant to glutamate-induced excitotoxicity. Herein we provide an overview of ipRGCs and discuss the injury-resistant character of these neurons under certain pathological and experimental conditions.

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          Diminished pupillary light reflex at high irradiances in melanopsin-knockout mice.

          In the mammalian retina, a small subset of retinal ganglion cells (RGCs) are intrinsically photosensitive, express the opsin-like protein melanopsin, and project to brain nuclei involved in non-image-forming visual functions such as pupillary light reflex and circadian photoentrainment. We report that in mice with the melanopsin gene ablated, RGCs retrograde-labeled from the suprachiasmatic nuclei were no longer intrinsically photosensitive, although their number, morphology, and projections were unchanged. These animals showed a pupillary light reflex indistinguishable from that of the wild type at low irradiances, but at high irradiances the reflex was incomplete, a pattern that suggests that the melanopsin-associated system and the classical rod/cone system are complementary in function.
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            Role of melanopsin in circadian responses to light.

            Melanopsin has been proposed as an important photoreceptive molecule for the mammalian circadian system. Its importance in this role was tested in melanopsin knockout mice. These mice entrained to a light/dark cycle, phase-shifted after a light pulse, and increased circadian period when light intensity increased. Induction of the immediate-early gene c-fos was observed after a nighttime light pulse in both wild-type and knockout mice. However, the magnitude of these behavioral responses in knockout mice was 40% lower than in wild-type mice. Although melanopsin is not essential for the circadian clock to receive photic input, it contributes significantly to the magnitude of photic responses.
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              Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors.

              Circadian rhythms of mammals are entrained by light to follow the daily solar cycle (photoentrainment). To determine whether retinal rods and cones are required for this response, the effects of light on the regulation of circadian wheel-running behavior were examined in mice lacking these photoreceptors. Mice without cones (cl) or without both rods and cones (rdta/cl) showed unattenuated phase-shifting responses to light. Removal of the eyes abolishes this behavior. Thus, neither rods nor cones are required for photoentrainment, and the murine eye contains additional photoreceptors that regulate the circadian clock.
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                Author and article information

                Journal
                7605074
                6087
                Neuroscience
                Neuroscience
                Neuroscience
                0306-4522
                1873-7544
                31 October 2015
                10 November 2014
                22 January 2015
                08 November 2015
                : 284
                : 845-853
                Affiliations
                [a ]Guangdong-HongKong-Macau Institute of CNS Regeneration, Jinan University, Guangdong, PR China
                [b ]Guangdong Medical Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou, PR China
                [c ]GHM Collaboration and Innovation Center for Tissue Regeneration and Repair, Jinan University, Guangzhou, PR China
                [d ]Department of Ophthalmology, University of Hong Kong, Hong Kong
                [e ]School of Veterinary Medicine and Biomedical Sciences, University of Nebraska, Lincoln, NE 68583, USA
                [f ]Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA
                Author notes
                [* ]Correspondence to: K.-F. So, GHM Institute of CNS Regeneration, Jinan University, 601 West Huangpu Avenue, Guangzhou 510632, Guangdong, PR China. Tel: +86-20-85228362; fax: +86-20-85223563. hrmaskf@ 123456hku.hk (K.-F. So)
                Article
                NIHMS734810
                10.1016/j.neuroscience.2014.11.002
                4637166
                25446359
                c48c81d9-bc60-47b4-aef2-bb7aac708829

                This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/3.0/).

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                Neurosciences
                melanopsin,intrinsically photosensitive retinal ganglion cell,injury,survival
                Neurosciences
                melanopsin, intrinsically photosensitive retinal ganglion cell, injury, survival

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