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Jinnan Yang, Harris Ripps, Wen Shen; Neural remodeling in the FVB/N mouse. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4376.
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FVB/N albino mice undergo photoreceptor degeneration during the early stages of retinal development. Our preliminary studies have shown that within 21 days the rods appear to be completely destroyed whereas some cones have survived. The purpose of this study was to characterize the neuronal rewiring process of second-order neurons that results from this rapid photoreceptor degeneration.
Various antibodies were used to detect structural changes of rods, cones, horizontal and bipolar cells of the FVB/N mice during early development, i.e., at age p7 to p21 days. H&E staining was used to detect the loss of cells in the outer and inner nuclear layer, and the light responses of rods and cones were elicited by green (520nm) and blue (380nm) stimuli, recorded in the extracellular space of the intact retina at the various ages.
We show that rods start to degenerate as early as day p7, about 50% have degenerated at p14, and almost all are gone by day p21. A significant loss of rods is accompanied by a gradual degeneration of M- and S-cone at day p14. Rod and cone degeneration did not reduce the densities of second order neurons (bipolar and horizontal cells) at the stages of retinal development. However, the microstructure of the dendritic regions of the second-order cells was significantly altered: rod-bipolar cells lacked dendrites by p21, but their axon terminals were unaffected. Photoreceptor degeneration seems to have far less effect on the structures of cone-bipolar cells as late as day p34. In addition, we noted that by day p21, some horizontal cells develop long processes that project to the inner plexiform layer.
This study provides valuable information toward a better understanding of the neural rewiring process of second-order retinal neurons during rapid rod degeneration. In addition to other rod-degenerative models, FVB/N is a unique model ideally suited for study and for the development of new therapeutic measures to ameliorate the blindness caused by photoreceptor degeneration.
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