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Molecular Studies of the Choriocapillaris in AMD

AMD 脉络膜毛细血管的分子研究

基本信息

批准号：
10541173
负责人：
Robert Foster Mullins
金额：
$ 38.63万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-01 至 2026-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10541173
关键词：
Address Affect Age related macular degeneration Atrophic Behavior Biochemical Blindness Blood Vessels Blood capillaries Categories Cells Cessation of life Choroid Choroidal Neovascularization Communities Complement Complement Membrane Attack Complex Complex Cytolysis Data Disease Drusen Endothelial Cells Extracellular Matrix Degradation Exudative age-related macular degeneration Eye Functional disorder Genes Health Histologic Human ICAM1 gene Imaging Techniques Immunofluorescence Immunologic In Situ Hybridization In Vitro Individual Inflammatory Injury Label Lentivirus Mediating Molecular Molecular Profiling Mus Nonexudative age-related macular degeneration PECAM1 gene Phenotype Photoreceptors Population Preparation Process Proliferating Public Health Research Resolution Retina Small Interfering RNA Structure of retinal pigment epithelium Thick complement system geographic atrophy human RNA sequencing induced pluripotent stem cell insight knowledge translation macula migration new technology normal aging preservation programs retinal damage single-cell RNA sequencing transcriptome transcriptomics

项目摘要

ABSTRACT Age-related macular degeneration (AMD) is a common cause of severe vision loss. Recent studies have shown that a layer of capillaries called the choriocapillaris is affected in AMD, both in “dry” AMD in which the blood vessels degenerate, depriving the retina of nourishment, and in “wet” AMD in which the cells become activated to grow abnormally, damaging the retina. To a large extent the biochemical changes in the choriocapillaris that accompany AMD are poorly understood. In this proposal we will study how a gene that is affected by the complement system and is enriched in AMD cells contributes to the processes associated with the choriocapillaris in AMD. We will also utilize a new technology (single cell RNA-sequencing) to discover the molecular signatures of endothelial cells from the choroid at the single cell level of resolution in health and different forms of AMD. A better understanding of how these cells are altered in disease will provide insight into how to protect them from damage and death.

摘要老年性黄斑变性(AMD)是导致严重视力丧失的常见原因。最近的研究表明显示在AMD中有一层称为脉络膜毛细血管的毛细血管受到影响，这两种情况在AMD中都是“干性”的。血管退化，剥夺视网膜的营养，而在湿性黄斑变性中，这些细胞会被激活，异常生长，从而损害视网膜。在很大程度上，生化 AMD伴发的脉络膜毛细血管的变化还知之甚少。在本提案中，我们将研究受补体系统影响并在AMD细胞中富含的基因如何有助于 AMD中与脉络膜毛细血管相关的突起。我们还将利用一项新技术(单项细胞RNA测序)，以发现脉络膜中内皮细胞的分子特征单细胞水平的分辨率在健康和不同形式的AMD。更好地理解这些细胞在疾病中的变化将为如何保护它们免受损害和死亡提供洞察力。