RETINOGEOGRAPHIC DISTRIBUTION OF SECRETED RETINOSCHISIN

分泌性视网膜分裂素的视网膜地理分布

• 批准号: 8357820
• 负责人: MARTHA NEURINGER
• 金额: $ 3.63万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357820
• 关键词: Adolescence; Adult; Affect; Animal Model; Biodistribution; Cells; Clinical Trials; Funding; Gene Transduction Agent; Genes; Grant; Human; Inherited; Mutation; National Center for Research Resources; Patients; Photoreceptors; Prevention; Primates; Principal Investigator; Proteins; Research; Research Infrastructure; Resources; Retinal; Retinal Degeneration; Retinal Detachment; Rodent; Route; School-Age Population; Source; United States National Institutes of Health; Vision; Visual Acuity; Vitreous Hemorrhage; X-Linked Retinoschisis; XLRS1 protein; cost; infancy; male; nonhuman primate; safety testing; vector

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 X连锁视网膜劈裂症（XLRS）是一种影响年轻男性的遗传性视网膜变性。 它是由正常视网膜功能所需的基因（视网膜分裂素或 RS1）突变引起的。 患者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。 在先前对 XLRS 啮齿动物模型的研究中，使用 AAV-RS1 基因治疗载体进行治疗可导致视网膜功能逐步且长期改善，并预防视网膜细胞变性。该项目正在测试 AAV-RS1 载体的安全性和生物分布，该载体通过视网膜下或玻璃体内注射到非人类灵长类动物中，这是计划对这种可能挽救视力的新疗法进行人体临床试验之前的关键最后一步。 结果表明，两种递送途径均将 RS1 转导至光感受器，并导致分泌性视网膜裂素蛋白的表达。