Delivering protection for photoreceptors
Retinitis pigmentosa (RP) is a retinal degenerative disease that is characterized by depletion of rod photoreceptors followed by the loss of cone cells. The majority of RP-associated mutations are in genes encoding rod-specific proteins, and the distinct progression of this disease suggests that rod function is required for cone photoreceptor maintenance. Rod-derived cone viability factor is generated as two distinct isoforms; RdCVF, a truncated form that promotes cone survival, and RdCVFL, which has oxioreductase activity; however, the specific functions of these proteins in the retina are not clear. Leah Byrne and colleagues at University of California Berkeley used adeno-associated virus-mediated (AAV-mediated) approaches to evaluate the specific effects of RdCVFL and RdCVF in murine RP models. Both systemic and intravitreal delivery of RdCVF rescued cone photoreceptors in RP mice, but did not restore rod cells. In contrast, RdCVFL expression early in the course of disease prolonged rod function and decreased cellular oxidative stress, but did not have any protective effect on cone cells. The results from this study demonstrate that the 2 isoforms of rod-derived cone viability factor differentially protect photoreceptors and suggest that RdCVF gene therapy has potential for prolonging vision in retinal degenerative diseases. The accompanying image shows a retinal section from a WT mouse following systemic delivery of a control GFP-expressing AAV vector, demonstrating delivery of the vector to multiple cells within the layers of the retina.
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Abstract
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Authors
Leah C. Byrne, Deniz Dalkara, Gabriel Luna, Steven K. Fisher, Emmanuelle Clérin, Jose-Alain Sahel, Thierry Léveillard, John G. Flannery
Copyright © 2017 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)