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:
  • 金额:
    $ 23.75万
  • 依托单位:
  • 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

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.
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:
  • 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
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Eric D Nudleman其他文献

Eric D Nudleman的其他文献

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{{ truncateString('Eric D Nudleman', 18)}}的其他基金

Cellular and Molecular Mechanisms of Retinal Fibrosis
视网膜纤维化的细胞和分子机制
  • 批准号:
    10819024
  • 财政年份:
    2023
  • 资助金额:
    $ 23.75万
  • 项目类别:

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