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。此外，恒河猴和日本猕猴都会出现与人类AMD非常相似的症状，我们已经在恒河猴身上证实了两个与人类相同的遗传风险因素。AMD非人类灵长类动物模型的出现使几种有希望的治疗方法的测试成为可能，包括基因治疗、干细胞治疗、生长因子和营养干预，以及视网膜退化机制的研究。该项目的目标是继续使用几种互补的方法来表征这些模型：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和干细胞疗法的可行性、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。在过去的一年里，研究继续确定遗传因素，测试基因疗法和干细胞疗法的可行性和安全性，并描述缺乏饮食叶黄素和n-3脂肪酸的猴子视网膜功能的变化，这两种营养素被认为可以降低AMD的风险。

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. 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 thesenonhuman 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 function in monkeys lacking dietary xanthophylls and n-3 fatty acids, two nutrients thought to lower the risk of AMD.