AGE RELATED MACULOPATHY--DRUSEN BIOGENESIS

描述（改编自申请人的摘要）：AMD的特征在于 中央视野逐渐丧失 由于萎缩性、渗出性和/或出血性变化， 黄斑。 没有药物治疗显示出对 预防、阻止或逆转与AMD相关的视力丧失。 拟议的研究主要集中在玻璃疣，这是 细胞外物质的积累，发展之间的视网膜 色素上皮（RPE）及其血液供应，脉络膜毛细血管。 相对而言，人们对这种物质的起源和组成知之甚少。 玻璃疣，即使玻璃疣存款被广泛认为是一种 严重的风险因素，发展萎缩和 渗出性AMD。 玻璃疣成分的初步研究已经导致 鉴定特定的Drusen相关分子（DRAM），许多 其中包括循环血浆蛋白和已知的参与者 纤维蛋白溶解、血栓形成、炎症和/或免疫过程 反应 在这项建议中，重点是玻璃疣的生物发生， 在视网膜色素上皮-脉络膜中鉴定DRAM的配体 跨细胞途径参与DRAM沉积。 实验 细胞系在这以及两个同伴的建议是设计 明确眼玻璃疣与脉络膜相关性 异常，以及随后发展为萎缩性AMD。 这样 这样做，申请人希望建立一个概念框架， 对病因进行更多的基础和临床研究， 预防AMD。

DESCRIPTION (Adapted from applicant's abstract): AMD is characterized by the progressive loss of vision in the central visual field attributable to atrophic, exudative and/or hemorrhagic changes in the macula. No pharmacologic treatment has been shown to be effective in preventing, arresting, or reversing loss of vision associated with AMD. The proposed research has focused primarily on drusen, which are accumulations of extracellular material that develop between the retinal pigment epithelium (RPE) and its blood supply, the choriocapillaris. Relatively little is known about the origin or the composition of drusen, even though drusen deposits are considered widely as a significant risk factor for the development of both atrophic and exudative AMD. Preliminary studies of drusen composition have led to the identification of specific drusen-associated molecules (DRAMs), many of which are circulating plasma proteins and known participants in the processes of fibrinolysis, thrombosis, inflammation, and/or the immune response. In this proposal, the emphasis is on drusen biogenesis, the identification of the ligands for DRAMs in the RPE-choroid in the transcellular pathways involved in DRAM deposition. The experimental cell line in this as well as the two companion proposals are designed to clarify the relationship between ocular drusen, related choroidal abnormalities, and the subsequent development of atrophic AMD. In so doing, the applicants hope to establish a conceptual framework for pursuing additional basic and clinical research into the causes and prevention of AMD.