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E. Strettoi, II, E. Novelli, F. Mazzoni; Effects of Photoreceptor Degeneration on Ganglion Cell Morphology: The rd10/Thy1-GFP Mouse. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2490.
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© ARVO (1962-2015); The Authors (2016-present)
Retinitis Pigmentosa (RP), a family of inherited diseases leading to progressive photoreceptor death, is one of the major causes of blindness in the world, with no cure yet. Retinal ganglion cells (RGCs) represent the last hope to restore vision in RP by means of epiretinal prostheses. Aim of this project is to assess the retention of the morphology and synaptic architecture of RGCs in a mouse model of RP at various stages of the disease.To this purpose, we generated a transgenic mouse, rd10/Thy1-GFP, by crossing GFP-M mice, (Feng et al, 2000), in which GFP is expressed in a small population of RGCs of various types, and rd10 mice, a model of autosomal recessive RP with a missense mutation of the ß-subunit of the rod-specific phosphodiesterase gene (Chang et al, 2002).
Animals were treated in accordance with ARVO and institutional guidelines. Both rd10 and Thy1-GFP mice were on a C57Bl6 background. Genotypes were determined by PCR. Immunolabeling with anti-GFP antibodies was performed on retinal whole-mounts from animals of 1 to 9 months of age. Retinas were counterstained with ethidium homodimer-1. RGC images were acquired by confocal microscopy, then analyzed and quantified with Metamorph and NeuroLucida softwares.
In rd10/Thy1-GFP mice, all the RGC types described by Sun et al, 2002, were represented; displaced RGC were frequently encountered. At 3 months of age, RGCs were undistinguishable from those of homogeneous type and eccentricity found in wt, control animals. At 7 months, RGCs from mutants mice displayed minor morphological modifications of the dendritic arborizations, with a loss of complexity of the branches of higher order. Numerous pycnotic profiles were observed in the GC layer.
Because photoreceptor degeneration does not overlap to retinal development, rd10 mice mimic closely human RP. When rod degeneration occurs (between P20 and P35), vascular regression also takes place. Our follow-up study suggests that RGCs become affected from the slow, transynaptic effects of photoreceptor degeneration, more than from the vascular changes. The alterations found in RGCs are similar to the secondary changes we previously described for horizontal and bipolar cells in rd10 mutant mice, in the sense that a progressive atrophy of the dendritic arborizations occurs. However, the remodelling of RGCs dendritic arbors seems remarkably slow, compared to both photoreceptor degeneration and remodelling of bipolar and horizontal cells. This suggests that the rd10 mutant is a good model to test the possibility of restoration therapies based upon the preservation of RGCs.
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