RETINOGEOGRAPHIC DISTRIBUTION OF SECRETED RETINOSCHISIN

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 X连锁视网膜劈裂症(XLRS)是一种遗传性视网膜变性，影响年轻男性。它是由正常视网膜功能所必需的基因(视黄醇或RS1)突变引起的。病人在婴儿期或学龄期视力不佳。视力通常在青少年时期恶化，然后稳定下来，直到成年后并发玻璃体出血或视网膜脱离。在之前对XLRS啮齿动物模型的研究中，AAV-RS1基因治疗载体的治疗导致视网膜功能的渐进性和长期改善，并防止视网膜细胞退化。该项目正在测试AAV-RS1载体的安全性和生物分布，将其注射到非人类灵长类动物的视网膜下或玻璃体内，作为这一潜在挽救视力的新疗法计划中的人类临床试验之前的关键最后一步。结果表明，这两种途径都将RS1转导到光感受器，并导致分泌的视黄醇蛋白的表达。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. X-linked retinoschisis (XLRS) is an inherited form of retinal degeneration affecting young males. It is caused by mutations in a gene (retinoschisin or RS1) that is required for normal retinal function. Patients present with poor vision in infancy or at school age. Visual acuity usually worsens during the teenage years and then stabilizes until complicated by vitreous hemorrhage or retinal detachment during adulthood. In a previous study in a rodent animal model of XLRS, treatment with an AAV-RS1 gene therapy vector resulted in progressive and long-term improvement in retinal function and prevention of retinal cell degeneration. This project is testing the safety and biodistribution of AAV-RS1 vector, injected either subretinally or intravitreally in nonhuman primates, as a critical final step prior to a planned human clinical trial of this potentially sight-saving new therapy. Results indicate that both routes of delivery transduced RS1 to photoreceptors and resulted in expression of the secreted retinoschisin protein.