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（由适用提供）：正常的视网膜脉管系统灌注神经感觉视网膜的黄斑，同时避免干扰图像分辨率。血管和/或血管泄漏的异常生长在预性过早（ROP），糖尿病患者视网膜病变（DR），正宗老年相关的黄斑变性（AMD）和血管闭塞的主要原因是视力丧失的主要原因。新的视网膜视频的形成，稳定和回归涉及多个细胞和固体因素。在细胞成分中，视网膜星形胶质细胞（RAC）在主要视网膜脉管系统的内皮播种中起重要作用。但是，星形胶质细胞 - 内皮细胞相互作用的机制尚不完全理解。该提案研究了一种新的机制，其中RACS释放的外泌体靶向内皮细胞，并导致正常的残留血管发育。 To test our hypothesis that molecules in RAC exosomes are important in the development of normal residual vasculature, as well as the inhibition of aberrant residual angiogenesis, we will 1) test the effect of exosomes from murine postnatal day 2 (P2) RACs (developing RAC exosomes) on proliferation, migration and tube formation using retinal endothelial cells; 2）确定发育中的RAC外泌体是否可以挽救低氧血症引起的异常血管生成[即氧诱导的视网膜病（OIR）]； 3）确定这些外泌体的血管生成特征是否反映了它们的功能。从这些结果中得出的信息将进一步了解RAC外泌体在正常残留脉管系统的开发和维持中的作用。这些观察结果可能导致新的治疗方法来控制异常的残留血管生成。