NONHUMAN PRIMATE MODELS OF RETINAL DISEASE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 老年性黄斑变性(AMD)是60岁以上成年人视力丧失的主要原因。黄斑是视网膜的专门区域，位于锐利的中央视觉之下，只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的疾病提供准确的模型。其他常见的遗传性视网膜疾病，如视网膜色素变性和Usher综合征，不会选择性地影响黄斑，但在这些疾病中，非人类灵长类动物模型对于理解保护黄斑和中心视力的因素将是唯一有价值的，这是一个主要的治疗目标。AMD的非人类灵长类动物模型的可获得性将使几种有前景的治疗方法的测试成为可能，包括基因治疗、视网膜移植、生长因子和营养干预，以及视网膜退化机制的研究。该项目的目标是使用几种互补的方法开发AMD的非人类灵长类动物模型：1)在ONPRC猕猴群体中鉴定患有自然发生的黄斑疾病的猴子；2)确定导致这种疾病的基因突变或易感因素和基因表达变化；3)测试视网膜基因疗法的可行性、安全性和有效性；以及4)测试可能保护黄斑免受黄斑变性影响的长期、受控饮食干预的效果。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. Other common inherited retinal diseases such as retinitis pigmentosa and Usher syndrome do not selectively affect the macula, but in these diseases also, a nonhuman primate model would be uniquely valuable for understanding the factors involved in preservation of the macula and central vision, a primary therapeutic goal. Availability of a nonhuman primate model of AMD would make possible tests of several promising therapeutic approaches, including gene therapy, retinal transplantation, growth factors and nutritional interventions, as well as studies of the mechanisms underlying retinal degeneration. This project's objective is to develop a nonhuman primate model for AMD 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 4) testing the effects of long-term, controlled dietary interventions that may protect the macula from macular degeneration.