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H.M. Cooper, O. Dkhissi-Benyahya, C. Rieux, R. Hut, W. de Vanssay; A New Cone in Human Retina . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2857.
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Purpose: Recent studies have shown that a subset of retinal ganglion cells that contain melanopsin are intrinsically photosensitive (Berson et al., 2002 Science 295, 1070-3). These cells project almost exclusively to the suprachiasmatic nucleus, suggesting their involvement in the photic entrainment of circadian rhythms. This study is aimed to define the presence of melanopsin-positive neurons in human retina in order to determine the involvement of this pigment in human circadian photoreception. Methods: Human eyes were obtained from donors and fixed after death by the department of Anatomy (University of Lyon, UCBL1) under approval of the Institutional Human Subjects Committee. Anti-melanopsin immunohistochemistry was performed on free floating sections (20 µm) of human retina. Results: Melanopsin is expressed in a sub-population of retinal ganglion cells in humans. The sparse and regular distribution is identical to that of melanopsin expressing ganglion cells in rodents and macaque (Provencio et al, J Neurosci 20, 600-5). Melanopsin also stains positively a small population of human cones. The melanopsin positive label is restricted to the cone outer segments. In order to determine whether melanopsin could be co-expressed with other opsins we used double label immunohistochemistry with specific antibodies directed against SW and MW/LW opsins. Confocal microscopy clearly shows that none of the melanopsin-positive cones contain either SW or MW/LW opsins. These melanopsin expressing cones are mainly located in the peripheral region of the retina and their density is approximately 10% of that of the SW cones. Conclusions: The results show the presence of a new type of cone photoreceptor in human retina, which stains positively with anti-melanopsin antibody and is devoid of MW/LW and SW opsins. Melanopsin expressing ganglion cells are considered to play a role in a broad range of non-visual irradiance detection processes due to their intrinsic photosensitivity and projections to structures mediating circadian rhythms, pupillary reflex, and seasonal rhythms. A similar role can be hypothesized for melanopsin in the human retina. The unexpected localization of melanopsin in cones raises the question of additional roles in human photoreceptive mechanisms.
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