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：
8752902
负责人：
Robert Foster Mullins
金额：
$ 37.75万
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/8752902
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 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 public health relevance 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）：与年龄相关的黄斑变性（AMD）是失明的主要原因，其特征是视网膜上皮上皮细胞 - 金乳果皮界面的病理变化。我们最近发现，脉络膜毛细血管的血管丧失与AMD的最早临床迹象有关，并且血管密度降低和“幽灵”血管数量的增加与Drusen和其他子RPE沉积物的大小和数量有关。在脉络膜毛细血管水平上激活末端补体途径和膜攻击复合物（MAC）的形成可能是AMD血管损失的原因。在此提案中，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。确定保护脉络膜内皮细胞免受MAC介导的裂解的小分子；并开发和测试途径，以最终替代丢失的内皮细胞。我们预计这些目标的完成将导致对保护脉络膜早期脉络膜的机制有重要的新理解，这可能会导致这种盲目疾病的新疗法。