Choriocapillaris protection and replacement in AMD

AMD 中脉络膜毛细血管的保护和替代

基本信息

批准号：
10397546
负责人：
Robert Foster Mullins
金额：
$ 37.47万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10397546
关键词：
Affect Age related macular degeneration Animal Model Atrophic Autologous Biochemical Blindness Blood Vessels Bruch&apos s basal membrane structure Cell Death Cell physiology Cells Choroid Clinical Clustered Regularly Interspaced Short Palindromic Repeats Coculture Techniques Complement Complement Factor H Complement Membrane Attack Complex Cytolysis Deposition Disease Drusen Endothelial Cells Endothelium Eye Functional disorder Funding Genotype Goals Health Hemorrhage Histologic Human Imaging Techniques Imidazole Immune Individual Injections Injury Knowledge Lead Macular degeneration Mediating Methods Molecular Nonexudative age-related macular degeneration Pathogenesis Pathologic Pathology Patients Pharmaceutical Preparations Photoreceptors Physiological Play Preventive treatment Public Health Research Retina Risk Role Structure of retinal pigment epithelium Vision base blood damage cell injury complement pathway density genome editing geographic atrophy high risk induced pluripotent stem cell injured macula novel programs repaired response restorative treatment risk variant small molecule stem cells treatment strategy vascular bed

项目摘要

Abstract Age-related macular degeneration (AMD) is a major cause of blindness worldwide that is characterized by pathologic changes at the retinal pigment epithelium-choriocapillaris interface. We recently found that loss of endothelial cells of the choriocapillaris is related to 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. Compelling evidence suggest that 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 and AMD pathogenesis. In this proposal we seek to identify the molecular and cellular responses of choroidal endothelial cells injured by MAC; to evaluate small molecules that protect choroidal endothelial cells against MAC-mediated lysis; and to develop an autologous iPSC based choroidal endothelial cell replacement approach. We anticipate that completion of the aims outlined in this application will result in an important new understanding of disease pathophysiology, which will allow us to further develop treatments focused on protecting and replacing damaged blood vessels in AMD.

抽象的年龄相关性黄斑变性（AMD）是世界范围内导致失明的主要原因，其特点是我们最近发现视网膜色素上皮-脉络膜毛细血管界面的病理变化。脉络膜毛细血管内皮细胞的减少与 AMD 的最早临床症状有关，并且减少血管密度和“幽灵”血管数量的增加与玻璃疣和玻璃疣的大小和数量有关其他令人信服的证据表明，末端补体途径的激活和在脉络膜毛细血管水平形成膜攻击复合体（MAC）是导致血管损失和 AMD 发病机制。在本提案中，我们试图确定受损脉络膜内皮细胞的分子和细胞反应通过 MAC；评估保护脉络膜内皮细胞免受 MAC 介导的裂解的小分子；开发基于自体 iPSC 的脉络膜内皮细胞替代方法。我们预计，完成本申请中概述的目标将产生一个重要的新成果了解疾病病理生理学，这将使我们能够开发出进一步的治疗方法保护和替换 AMD 中受损的血管。