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：
8895955
负责人：
Robert Foster Mullins
金额：
$ 37万
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 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8895955
关键词：
Acute Affect Age Age related macular degeneration Animal Model Atrophic Biochemical Blindness Blood Vessels Bruch&apos s basal membrane structure Cell Death Cells Cessation of life Choroid Chronic Clinical Complement Complement Factor H Complement Membrane Attack Complex Cytolysis Deposition Development Disease Drusen Endothelial Cells Epithelial Eye Genotype Goals Health Human Imaging Techniques Immune system In Vitro Individual Injury Lead Lytic Macular degeneration Manuscripts Mediating Methods Molecular Molecular Profiling Mus Pathologic Patients Photoreceptors Play Preparation Preventive Public Health Research Retinal Pigments Role Staging Stem cells Structure of retinal pigment epithelium Testing Transplantation Vision base cell injury complement pathway density high risk induced pluripotent stem cell injured macula molecular imaging monolayer mouse model novel prevent programs repaired response restorative treatment risk variant small molecule tissue culture

项目摘要

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.

描述（由申请人提供）：年龄相关性黄斑变性（AMD）是失明的主要原因，其特征是视网膜色素上皮-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损失与AMD最早的临床症状有关，而血管密度的降低和“幽灵”血管数量的增加与玻璃疣和其他亚RPE沉积物的大小和数量有关。末端补体途径的激活和脉络膜毛细血管水平的膜攻击复合物 (MAC) 的形成是 AMD 血管损失的可能原因。在本提案中，我们试图确定 MAC 损伤的脉络膜内皮细胞的分子和细胞反应；鉴定可保护脉络膜内皮细胞免受 MAC 介导的裂解的小分子；并开发和测试最终替代丢失的内皮细胞的途径。我们预计，这些目标的完成将带来对早期 AMD 脉络膜保护机制的重要新认识，这可能会带来针对这种致盲疾病的新疗法。