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Exsomes derived from retinal astrocytes in the regulation of retinal vasculature

视网膜星形胶质细胞衍生的外泌体在视网膜血管系统调节中的作用

基本信息

批准号：
9040963
负责人：
HENRY Jerrold KAPLAN
金额：
$ 18.75万
依托单位：
UNIVERSITY OF LOUISVILLE
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9040963
关键词：
Adult Affect Age related macular degeneration Angiogenic Proteins Astrocytes Blindness Blood Vessels Caliber Cell Communication Cell membrane Cells Choroidal Neovascularization Development Diabetic Retinopathy Disease Endostatins Endothelial Cells Extravasation Exudative age-related macular degeneration Goals Growth Health Hemorrhage Hypoxemia Image Lasers Lead Life Lipids Maintenance Mediating Messenger RNA MicroRNAs Microglia Modeling Multivesicular Body Mus Neonatal Neurophysiology - biologic function Oxygen Parents Pathology Phase Phenotype Physiological Physiology Plasma Cells Play Proteins Proteomics Regulation Resolution Retina Retinal Retinal Diseases Retinopathy of Prematurity Role Staging Testing Tissue Inhibitor of Metalloproteinase-1 Vascularization Vesicle Visual Western Blotting angiogenesis base exosome macula migration nanoscale neovascular neurosensory novel novel therapeutics pigment epithelium-derived factor postnatal proliferative diabetic retinopathy retina blood vessel structure retinal angiogenesis tumor

项目摘要

DESCRIPTION (provided by applicant): The normal retinal vasculature perfuses the macula of the neurosensory retina while avoiding interference with image resolution. The abnormal growth of blood vessels and associated bleeding and/or vascular leakage in retinopathy of prematurity (ROP), diabetics retinopathy (DR), exudative aged-related macular degeneration (AMD), and vascular occlusions are major causes of vision loss. Multiple cellular and soluble factors are involved in the formation, stabilization and regression of new retinal vessels. Among the cellular components, retinal astrocytes (RACs) play an important role in endothelial seeding of the primary retinal vasculature. However, the mechanism of astrocyte- endothelial cell interaction is incompletely understood. This proposal investigates a novel mechanism in which exosomes released by RACs target endothelial cells and result in normal retinal vasculature development. To test our hypothesis that molecules in RAC exosomes are important in the development of normal retinal vasculature, as well as the inhibition of aberrant retinal angiogenesis, we will 1) test the effect of exosomes from murine postnatal day 2 (P2) RACs (developing RAC exosomes) on proliferation, migration and tubule formation using retinal endothelial cells; 2) determine whether developing RAC exosomes can rescue aberrant angiogenesis induced by hypoxemia [i.e. oxygen-induced retinopathy (OIR)]; and 3) determine whether the angiogenic profiles of these exosomes reflect their function. Information derived from these results will further our understanding of the role of RAC exosomes in the development and maintenance of normal retinal vasculature. These observations may result in novel therapy to control aberrant retinal angiogenesis.

描述(申请人提供)：正常的视网膜血管灌流神经感觉性视网膜的黄斑，同时避免干扰图像分辨率。早产儿视网膜病变(ROP)、糖尿病视网膜病变(DR)、渗出性老年性黄斑变性(AMD)和血管闭塞是导致视力丧失的主要原因。多种细胞因子和可溶性因子参与了视网膜新生血管的形成、稳定和消退。在细胞成分中，视网膜星形胶质细胞(RACs)在原发视网膜血管内皮细胞的种植中起着重要作用。然而，星形胶质细胞与内皮细胞相互作用的机制尚不完全清楚。这项建议研究了一种新的机制，即由RAC释放的外切体以内皮细胞为靶点，并导致正常的视网膜血管发育。为了验证我们的假设，即RAC外切体中的分子在正常视网膜血管系统的发育以及异常视网膜血管生成的抑制中起重要作用，我们将1)测试小鼠出生后第2天(P2)RAC外切体(正在发育中的RAC外切体)对利用视网膜内皮细胞增殖、迁移和形成小管的影响；2)确定发育中的RAC外切体是否可以挽救因低氧诱导的异常血管生成[即氧诱导视网膜病变(OIR)]；以及3)确定这些外切体的血管生成轮廓是否反映其功能。从这些结果中获得的信息将进一步加深我们对RAC外切体在正常视网膜血管系统的发育和维持中的作用的理解。这些观察结果可能导致控制异常视网膜血管生成的新疗法。