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H. Cheng, J. Yao, E. Filippova, B. Chang, J. Heckenlively, A. Swaroop; Subretinal Transplantation of Purifed Cone Precursors in Mouse Cone Degeneration Mutants. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5087.
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Post-mitotic rod precursors are able to integrate within the outer nuclear layer by subretinal transplantion and at least partially rescue rod function in rod degeneration models. Our goal is to test whether cone precursors are able to integrate into the degenerated retina and rescue cone function.
GFP positive cone precursors were purified from the Nrl-Ko-GFP mice by FACS analysis, and transplanted, at different time-points, into the subretinal space of the Crx::Nr2e3/WT (rod-only retina) and cone degenerative mouse models (Cnga3, Gnat2, and Pde6C mutants). ERGs were recorded to evaluate retinal function. Histology and immunohistochemistry were also performed.
Cone precursors from the Nrl-ko-GFP mice, collected at postnatal day 2-6, were able to undergo terminal differentiation in mutant retina when injected at P2-10 before retinal degeneration. Photopic ERGs showed improvement in the cone degenerative mouse (Cnga3 mutant), but not in the Crx::Nr2e3/WT mice. Immunohistochemistry revealed that the orientation of transplanted photoreceptors were reversed in the Crx::Nr2e3/WT mice and did not seem to form normal synapse with bipolar cells. Subretinal transplantations of GFP positive cells in adult degenerating retina and other cone degenerative mouse mutants (Pde6C and Gnat2) are in progress.
Our data suggest a possible (at least partial) rescue of cone phenotype in mouse models showing cone degeneration.
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