Loss of SPATA7 function causes the pathogenesis of Leber congenital amaurosis and retinitis pigmentosa. Spata7 knockout mice\nmimic human SPATA7ââ?¬â??related retinal disease with apparent photoreceptor degeneration observed as early as postnatal day 15\n(P15). To test the efficacy of adeno-associated virus (AAV)-mediated gene therapy for rescue of photoreceptor survival and function\nin Spata7 mutant mice, we employed the AAV8(Y733F) vector carrying hGRK1-driven full-length FLAG-tagged Spata7 cDNA to\ntarget both rod and cone photo receptors. Following subretinal injection of this vector, FLAG-tagged SPATA7 was found to\ncolocalize with endogenous SPATA7 in wild-type mice. In Spata7 mutant mice initially treated at P15, we observed improvement of\nphoto response, photoreceptor ultra structure and significant alleviation of photoreceptor degeneration. Furthermore, we performed\ntreatments at P28 and P56 and found that all treatments (P15-P56) can ameliorate rod and cone loss in the long term (1 year);\nhowever, none efficiently protect photo receptors from degeneration by 86 weeks of age as only a small amount of treated\nphoto receptors can survive to this time. This study demonstrates long-term improvement of photoreceptor function by AAV8\n(Y733F)-introduced Spata7 expression in a mouse model as potential treatment of the human disease, but also suggests that\ntreated mutant photo receptors still undergo progressive degeneration.
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