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Role of PDLIM1 in Retinal Vascular Leakage and Proliferation

PDLIM1 在视网膜血管渗漏和增殖中的作用

基本信息

批准号：
9902472
负责人：
Eric D Nudleman
金额：
$ 23.75万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9902472
关键词：
Address Affect Age American Animals Area Blindness Blood Blood - brain barrier anatomy Blood Vessels Blood-Retinal Barrier Brain Cell Culture Techniques Cells Child Childhood Colon Carcinoma Control Animal Data Developing Countries Development Diabetic Retinopathy Disease Doxycycline Edema Endothelial Cells Endothelium Epilepsy Exposure to Extravasation Fibrosis Functional disorder Gene Expression Profiling Genes Genetic Transcription Growth Hemorrhage Hypoxia Incidence Intention Ischemia Knock-out Knockout Mice Lead Low Birth Weight Infant Luciferases Mediating Mediator of activation protein Modeling Molecular Morbidity - disease rate Mouse Strains Mus Oxygen Peripheral Permeability Phenotype Proliferating Property Reporter Retina Retinal Detachment Retinal Diseases Retinopathy of Prematurity Role Seizures Stroke Survival Rate System Testing Time Traction Transfection Transgenic Mice Transgenic Organisms Traumatic Brain Injury Up-Regulation Vascular Diseases Vascular Endothelial Cell Vascular Endothelial Growth Factors Vascular Permeabilities Vascular Proliferation Visual WNT Signaling Pathway Work World Health Organization aging population beta catenin blind cytokine disease phenotype improved in vivo mouse model neonatal care neovascular neovascularization new therapeutic target overexpression premature prevent retina blood vessel structure retinal angiogenesis tissue culture transcription factor transcriptome

项目摘要

Abstract Retinopathy of Prematurity (ROP) is a potentially blinding condition of low birth weight premature children that affects over 50,000 children worldwide each year. The incidence of ROP is on the rise, primarily due to improvements in neonatal care in developing nations. The underlying pathophysiology of ROP is a consequence of ischemia of the peripheral retina. Ischemia can lead aberrant neovascularization at the border between the vascularized and non-vascularized retina. These vessels are incompetent and may lead to edema, bleeding, fibrosis, and can ultimately progress to a tractional retinal detachment and blindness. Importantly, parallel vascular changes are also responsible for visual morbidity in other diseases of the retinal vasculature, including diabetic retinopathy (DR), which affects 25.8 million Americans and is the leading cause of blindness in the working-age population. Changes in the function of the retinal vascular endothelial cells, including neovascularization and vascular leakage, are central to the disease phenotype, yet little is known about the molecular changes that occur in these cells that lead to their dysfunction. To investigate these molecular changes, we have purified the vascular endothelial cells during key timepoints in oxygen induced retinopathy (OIR), a mouse model of ischemic vasculopathy, and evaluated the transcriptome. These data identified PDLIM1 as a molecule that is upregulated specifically in the vascular endothelial cells at the time of leakage and proliferation. In tissue culture, expression of PDLIM1 results in a reduction of the barrier properties. We have now generated PDLIM1 knockout and overexpression mouse strains, and propose to test the role of PDLIM1 in retinal vascular permeability and proliferation. This work may identify PDLIM1 as a novel therapeutic target to prevent breakdown of the blood-retinal barrier and aberrant neovascularization in diseases of the retinal vasculature.

摘要

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Microcornea, Posterior Megalolenticonus, Persistent Fetal Vasculature, and Coloboma Syndrome Associated With a New Mutation in ZNF408.

DOI：
10.3928/23258160-20190401-10
发表时间：
2019-04
期刊：
Ophthalmic surgery, lasers & imaging retina
影响因子：
0
作者：
Geoffrey A. Weiner;E. Nudleman
通讯作者：
Geoffrey A. Weiner;E. Nudleman

IDENTIFICATION OF FACTORS RELATED TO SUBFOVEAL DETACHMENT SECONDARY TO EPIRETINAL MEMBRANE.

与视网膜前膜继发的凹下脱离相关的因素的识别。

DOI：
10.1097/iae.0000000000002056
发表时间：
2019
期刊：
Retina (Philadelphia, Pa.)
影响因子：
0
作者：
Muftuoglu,IlkayKilic;Lin,Tiezhu;Nudleman,Eric;Gaber,Raouf;Bartsch,Dirk-Uwe;Freeman,WilliamR
通讯作者：
Freeman,WilliamR