AAV-mediated gene replacement, either alone or in combination with physical and pharmacological agents, results in partial and transient protection from XXXX associated with @entity942 .

@entity39446 @entity19 @entity17425 @entity27763 @entity4700 @entity6391 @entity141 @entity528 @entity942
PURPOSE: Mutations in the @entity39446 gene cause recessive, severe @entity6391 ( @entity6391 ). @entity39446 encodes the b subunit of the rod-specific phosphodiesterase (bPDE), which, when absent, results in toxic levels of intracellular @entity141 and photoreceptor cell death. @entity141 blockers, such as @entity17425 , as well as light restriction, slow @entity528 in animal models of @entity942 . The goal of the study was to evaluate the efficacy of @entity4700 /5- or @entity4700 /8-mediated gene replacement in combination with @entity17425 and/or with light restriction in the @entity27763 @entity19 bearing homozygous @entity27763 mutations. METHODS: AAV vectors encoding either bPDE or EGFP were subretinally administered at postnatal day (P)2. @entity17425 was administered from P7 to P28. For light restriction, pregnant @entity27763 @entity19 were kept in a dark environment until their pups were 28 days old. All functional and histologic analyses were performed at P35. RESULTS: Significant morphologic photoreceptor protection was observed after subretinal administration of AAV vectors encoding EGFP. This protection further increased after administration of @entity4700 /8 or -2/5 encoding for bPDE and was not associated with significant functional improvement. Photoreceptor protection was higher after @entity4700 /8- than after @entity4700 /5-mediated delivery and was not significantly augmented by additional drug therapy and/or light restriction. The protective effect was lost after P35. CONCLUSIONS: In conclusion, more efficient gene transfer tools than those used in this study, as well as a better understanding of the disease pathogenesis, should be explored to increase the effect of gene replacement and to design gene-based strategies that block the apoptotic pathways activated by @entity942 .
