GENETICS OF MACULAR DEGENERATION

这项提案的总体目标是确定导致北卡罗来纳州黄斑病变的致病基因 并阐明导致黄斑变性的潜在分子机制。北 卡罗莱纳州黄斑营养不良(OMIM#136550)是一种常染色体显性、高度穿透性黄斑 以不同的表型为特征的退行性变，包括黄斑、黄斑、 萎缩和脉络膜新生血管。 设计了三个特定的目标来检验潜在的中心假设：基因的蛋白质产物 对于北卡罗来纳州的黄斑营养不良，被称为MCDR1，是正常功能所必需的 黄斑变性表型与MCDR1基因突变有关。这个 三个具体目标是：1)确定北卡罗来纳州黄斑营养不良症(MCDR1)的疾病基因；2) 研究MCDR1mRNA和蛋白的表达谱及功能；3)研究MCDR1的生物学特性 MCDR1在小鼠体内的作用。 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 退化并伴有视力丧失。此外，北卡罗来纳州黄斑营养不良症具有重要的临床特征。 老年性黄斑变性(AMD)的特征。玻璃斑疹是AMD和脉络膜的特征 新生血管(CNV)是AMD最重要的并发症之一。他们两个都出现在 北卡罗来纳州黄斑营养不良患者。因此，这些观察结果使北卡罗来纳州变得黄斑 营养不良是AMD独特的遗传模式.了解MCDR1的分子机制应 为黄斑变性的发病机制提供了新的见解。 MCDR1基因可能会增加我们对视网膜细胞生物学和玻璃体形成的了解 很特别。最后，这项研究可能为寻求治疗黄斑的新策略提供信息。 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.