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I Provencio, DM Berson, RC Richardson, MD Rollag, AM Castrucci; Melanopsin Immunoreactivity in Retinal Ganglion Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1363.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Retinal ganglion cells (RGCs) that project to the hypothalamic suprachiasmatic nuclei (SCN) mediate photoentrainment of circadian rhythms. These RGCs may be circadian photoreceptors because many of them are intrinsically photosensitive and many contain mRNA for melanopsin, a likely photopigment. We aim to gain an understanding of this photoreceptive system by morphologically characterizing this unique subclass of RGCs. Methods: We used a very specific antiserum raised against a peptide corresponding to the 15 N-terminal amino acids of mouse melanopsin. This antiserum was used to immunohistochemically label melanopsin-containing RGCs in sectioned mouse retinas and flat-mounted mouse and rat retinas. Results: In mouse retina, a single type of RGC was strongly melanopsin immunoreactive. Staining marked the soma and full dendritic arbor, and defined a quasi-regular mosaic that tiled the entire retina. Dendritic arbors were sparsely branched, large (∼400 microns in diameter), and arborized almost entirely within the outermost stratum of the inner plexiform layer (S1 of the IPL). Some members of the mosaic had somas displaced to the inner nuclear layer but were identifiable as RGCs from axonal staining. In rat retina, very similar RGCs were melanopsin immunopositive and were morphologically indistinguishable from the intrinsically photosensitive ganglion cells innervating the SCN. In the mouse, a second group of neurons of the ganglion cell layer were melanopsin immunopositive. They were more weakly stained, with dendrites arborizing in the innermost IPL (S5 of the IPL). Melanopsin labeling was highly specific and could be abolished by preadsorption of the antiserum with the N-terminal peptide. Preadsorption with a C-terminal peptide had no effect. Conclusion: We have identified a photoreceptive net within the inner retina of mammals which is composed of melanopsin-rich dendrites arising from a small subset of RGCs. This novel photoreceptive apparatus may fulfill the need of the circadian system for a broad-capture integrating photoreceptive system.
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