NONHUMAN PRIMATE MODELS OF RETINAL DISEASE

视网膜疾病的非人类灵长类动物模型

• 批准号: 8357729
• 负责人: MARTHA NEURINGER
• 金额: $ 5.82万
• 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/8357729
• 关键词: Adult; Age related macular degeneration; Age-Years; Area; Blindness; Complex; Dietary Intervention; Disease; Funding; Gene Expression; Gene Mutation; Genes; Genetic; Genetic Predisposition to Disease; Grant; Growth Factor; Human; Japanese Population; Long-Term Effects; Macaca; Macaca mulatta; Macular degeneration; Modeling; Monkeys; National Center for Research Resources; Nutrient; Omega-3 Fatty Acids; Primates; Principal Investigator; Research; Research Infrastructure; Resources; Retina; Retinal; Retinal Degeneration; Retinal Diseases; Risk; Safety; Source; Structure; Syndrome; Testing; Therapeutic; United States National Institutes of Health; Vision; Work; Xanthophylls; cost; disorder of macula of retina; gene therapy; genetic risk factor; macula; nonhuman primate; stem cell therapy

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. Age-related macular degeneration (AMD) is the leading cause of vision loss in adults over 60 years of age. The macula, the specialized area of the retina that underlies sharp central vision, is present only in human and nonhuman primates, so that only nonhuman primates can provide an accurate model for this complex disease. Furthermore, both rhesus and Japanese macaques develop syndromes closely resembling human AMD, and in rhesus we have confirmed two genetic risk factors that are shared with humans. Availability of these nonhuman primate models of AMD makes possible tests of several promising therapeutic approaches, including gene therapy, stem cell therapy, growth factors and nutritional interventions, as well as studies of the mechanisms underlying retinal degeneration. This project's objective is to continue to characterize these models using several complementary approaches: 1) identifying monkeys with naturally-occurring macular disease in the ONPRC macaque colonies; 2) determining the genetic mutations or susceptibility factors and gene expression changes underlying this disease; 3) testing the feasibility, safety and efficacy of retinal gene therapies and stem cell therapies; and 4) testing the effects of long-term, controlled dietary interventions that may protect the macula from macular degeneration. Studies in the past year continued the work of defining genetic factors, tested the feasibility and safety of both gene and stem cell therapies, and characterized changes in retinal structure and function in monkeys lacking dietary xanthophylls and n-3 fatty acids, two nutrients thought to lower the risk of AMD.

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。 年龄相关性黄斑变性 (AMD) 是 60 岁以上成年人视力丧失的主要原因。黄斑是视网膜的特殊区域，是锐利中央视力的基础，仅存在于人类和非人类灵长类动物中，因此只有非人类灵长类动物才能为这种复杂疾病提供准确的模型。 此外，恒河猴和日本猕猴都会出现与人类 AMD 非常相似的综合征，并且在恒河猴中，我们已经证实了两个与人类共有的遗传风险因素。这些AMD非人类灵长类动物模型的出现使得测试几种有前景的治疗方法成为可能，包括基因疗法、干细胞疗法、生长因子和营养干预，以及视网膜变性机制的研究。该项目的目标是继续使用几种补充方法来表征这些模型：1) 识别 ONPRC 猕猴中患有自然发生的黄斑疾病的猴子 殖民地； 2）确定导致该疾病的基因突变或易感因素以及基因表达变化； 3）测试视网膜基因疗法和干细胞疗法的可行性、安全性和有效性； 4) 测试长期、受控饮食干预措施的效果，以防止黄斑变性。去年的研究继续进行遗传因素的定义工作，测试了基因和干细胞疗法的可行性和安全性，并描述了缺乏膳食叶黄素和 n-3 脂肪酸（这两种营养素被认为可以降低 AMD 风险）的猴子视网膜结构和功能的变化。