Choriocapillaris Protection and Replacement in AMD

描述（由申请人提供）：视网膜相关性黄斑变性（AMD）是致盲的主要原因，其特征在于视网膜色素上皮-脉络膜毛细血管界面的病理变化。我们最近发现脉络膜毛细血管的血管缺失与AMD的早期临床症状有关，并且血管密度降低和“幽灵”血管数量增加与玻璃疣和其他RPE下沉积物的大小和数量有关。终末补体途径的激活和膜攻击复合物（MAC）在脉络膜毛细血管水平的形成是AMD血管损失的可能原因。在这个建议中，我们试图确定的分子和细胞的反应脉络膜内皮细胞MAC损伤，以确定小分子，保护脉络膜内皮细胞对MAC介导的溶解，并开发和测试的途径，最终更换丢失的内皮细胞。我们预计，这些目标的完成将导致对早期AMD中保护脉络膜的机制的重要新理解，这可能导致这种致盲性疾病的新疗法。

DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) is a major cause of blindness that is characterized by pathologic changes at the retinal pigment epithelium-choriocapillaris interface. We recently found that vascular loss of the choriocapillaris is relatedto the earliest clinical signs of AMD, and that a reduced vascular density and increased number of "ghost" vessels are related to the size and number of drusen and other subRPE deposits. Activation of the terminal complement pathway and formation of the membrane attack complex (MAC) at the level of the choriocapillaris is a likely cause of vascular loss in AMD. In this proposal we seek to identify the molecular and cellular responses of choroidal endothelial cells injured by MAC; to identify small molecules that protect choroidal endothelial cells against MAC-mediated lysis; and to develop and test avenues for the eventual replacement of lost endothelial cells. We anticipate that completion of these aims will result in important new understanding of mechanisms of protecting the choroid in early AMD, which may lead to new therapies for this blinding disease.