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E.-J. Lee, G. Sun, N. Grzywacz; Expression of Melanopsin-Containing Ganglion Cells in Degenerative Retina. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4421.
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Mice lacking rods and cones can respond to environmental irradiance (Freedman et al., 1999; Lucas et al., 1999, 2001; Mrosovsky et al., 2001). The candidate photo-sensitive neurons mediating these responses are melanopsin retinal ganglion cells. We investigated the effects of photoreceptor degeneration on the distribution of melanopsin-positive ganglion cells in various stages of retinal-degeneration (RD) rats.
For control, Copenhagen rats (Harlan, Indianapolis, IN) of both sexes were used. For RD models, we used pigmented S334ter-line-3 transgenic rats expressing a mutated human rhodopsin. Rats were sacrificed at postnatal (P) days P90, P180, P300, and P600, being maintained on a daily 12 h light/dark cycle throughout their lifes. We studied the morphology, distribution, and circuitry of melanopsin-positive ganglion cells in the control and RD rats by immunocytochemistry.
In P90-control and P90-S334ter-line-3 transgenic retinas, the densities of melanopsin-immunoreactive cells in the ganglion cell layer (GCL) were similar. The densities peaked at 29 ± 4 cells/mm2 (mean ± standard deviation) around the optic disc towards the superior portion of the retinas. Later on (e.g., in P180-control retinas), the density fell slightly but significantly at the same region (to 21 ± 2 cells/mm2 at P180). Thus, in control animals, the number of melanopsin-immunoreactive cells declines with age. In contrast, in S334ter-line-3 retinas, the melanopsin-immunoreactivity labeled many more cells (e.g., 62 ± 4 cells/mm2 at P180). In addition, in later S334ter-line-3 retinas, melanopsin-immunoreactive bands in the Stratum 1 of the IPL were much stronger than those of control retinas. Hence, the density of these cells and of their dendritic processes increases significantly with age in RD. This increase appeared to be specific for this cell, because the thicknesses of the GCL in both control and RD rats were similar in control and S334ter-line-3 retinas.
A possible explanation for our data is that the RD rat produces photo-sensitive ganglion cells, i.e., melanopsin-containing ones, in response to outer-retinal photoreceptor cell loss.
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