GENETICS OF MACULAR DEGENERATION

这项建议的主要目的是确定一个疾病基因负责北卡罗来纳州黄斑 营养不良和阐明导致黄斑变性的潜在分子机制。北 卡罗莱纳黄斑营养不良（OMIM #136550）是一种常染色体显性遗传的高度外显性黄斑营养不良， 以可变表型为特征的变性，包括黄斑部的融合性玻璃疣，黄斑部的玻璃疣， 萎缩和脉络膜新生血管形成。 设计了三个具体的目标来检验潜在的中心假设：基因的蛋白质产物 对于北卡罗来纳州，称为MCDR 1的黄斑营养不良对于视网膜的正常功能是必不可少的。 并且黄斑变性表型与MCDR 1基因突变相关。的 三个具体目标是：1）鉴定北卡罗来纳州黄斑营养不良症的疾病基因，MCDR 1; 2） 研究MCDR 1的mRNA和蛋白表达谱及功能; 3）研究MCDR 1的生物学特性， MCDR 1在小鼠系统中的作用。 研究北卡罗来纳州黄斑营养不良的遗传基础很重要，因为它会导致青少年黄斑营养不良。 退化并伴有视力丧失。此外，北卡罗来纳州黄斑营养不良与其他黄斑营养不良有重要的临床意义。 年龄相关性黄斑变性（AMD）。玻璃疣是AMD和脉络膜疾病的标志。 新生血管（CNV）是AMD最重要的并发症之一。他们两人都在 患有北卡罗来纳州黄斑营养不良的患者。因此，这些观测结果使北卡罗来纳州成为黄斑区 营养不良是AMD的独特遗传模型。了解MCDR 1的分子机制应该 导致新的见解黄斑变性的发病机制。阐明了 MCDR 1基因可能会增加我们对视网膜细胞生物学和玻璃疣形成的理解。 特别的。最后，本研究可为寻求治疗黄斑变性的新策略提供信息， 退化

The broad objective of this proposal is to identify a disease gene responsible for North Carolina macular dystrophy and to elucidate the underlying molecular mechanisms that lead to macular degeneration. North Carolina macular dystrophy (OMIM #136550) is an autosomal dominant, highly penetrant macular degeneration characterized by variable phenotypes including confluent drusen in the macula, macular atrophy, and choroidal neovascularization. Three specific aims are designed to test the underlying central hypothesis: that the protein product of the gene for North Carolina macular dystrophy, designated as MCDR1, is essential for the normal function of the macula and that the macular degeneration phenotype is associated with mutations in the MCDR1 gene. The three specific aims are: 1) to identify the disease gene for North Carolina Macular Dystrophy, MCDR1; 2) to characterize the mRNA and protein expression profiles and function of MCDR1; 3) to study the biological effect of MCDR1 in a mouse system. It is important to study the genetic basis of North Carolina macular dystrophy, as it causes juvenile macular degeneration with visual loss. Furthermore, North Carolina macular dystrophy shares important clinical features with age-related macular degeneration (AMD). Drusen is a hallmark of AMD and choroidal neovascularization (CNV) is one of the most important complications of AMD. Both of them are present in patients with North Carolina macular dystrophy. Therefore, these observations make North Carolina macular dystrophy a unique genetic model for AMD. Understanding the molecular mechanisms of MCDR1 should lead to novel insights into the pathogenesis of macular degeneration. Elucidation of the function of the MCDR1 gene may increase our understanding of retinal cell biology in general and drusen formation in particular. Finally, this study may provide information for pursuing novel strategies for treatment ofmacular degeneration.