Regulation of Choroidal Neovascularization in Sorsby's Fundus Dystrophy

索尔斯比眼底营养不良中脉络膜新生血管的调节

基本信息

  • 批准号:
    9900004
  • 负责人:
  • 金额:
    $ 39.63万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-04-01 至 2021-05-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Sorsby fundus dystrophy (SFD) is a dominantly inherited, degenerative disease of the macula that is characterized by bilateral loss of central vision as a consequence of choroidal neovascularization (CNV). Specific mutations in the TIMP-3 gene involving exon 5 or the intron4-exon5 boundary have been shown to be causative. Early this year, the AMD consortium identified rare coding variants in the TIMP3 gene when analyzing 16,144 patients and 17,832 controls. In addition, they identified the first genetic association signal specific to wet AMD near MMP9. The clinical and histopathological similarities between AMD and SFD and the identification of variants in the matrix metalloproteinase pathway in AMD suggest that similar downstream effectors might be in play in both conditions. A better understanding of the pathophysiological mechanisms contributing to the CNV in SFD will provide information that could be potentially useful in AMD. In comparative studies using TIMP-3 deficient mice, S156CTIMP-3 transgenic mice and in vitro culture experiments we have determined that TIMP-3 partially inhibits angiogenesis by blocking the binding of VEGF to VEGR-2. S156C TIMP-3 mutant protein induces angiogenesis via VEGF and bFGF. We have also shown that the absence of functional TIMP-3 results in an accumulation of hyaluronan that regulates choroidal vasculature. Based on these results, we hypothesize that TIMP3 is required to control and localize matrix degradation in the RPE/choroid, and loss of TIMP3 function in this regards leads to an abnormality in growth factor/angiogenesis factor, increased HA signaling and neovascularization.
项目总结

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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BELA ANAND-APTE其他文献

BELA ANAND-APTE的其他文献

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{{ truncateString('BELA ANAND-APTE', 18)}}的其他基金

FGF and hyaluronan-mediated alterations in epithelial-mesenchymal transition and metabolism of RPE cells in Sorsby Fundus Dystrophy.
FGF 和透明质酸介导的索斯比眼底营养不良中 RPE 细胞上皮-间质转化和代谢的改变。
  • 批准号:
    10408757
  • 财政年份:
    2017
  • 资助金额:
    $ 39.63万
  • 项目类别:
FGF and hyaluronan-mediated alterations in epithelial-mesenchymal transition and metabolism of RPE cells in Sorsby Fundus Dystrophy.
FGF 和透明质酸介导的索斯比眼底营养不良中 RPE 细胞上皮-间质转化和代谢的改变。
  • 批准号:
    10636830
  • 财政年份:
    2017
  • 资助金额:
    $ 39.63万
  • 项目类别:
Role of Retinoic Acid in the Regulation of the Blood-Retinal Barrier.
视黄酸在血视网膜屏障调节中的作用。
  • 批准号:
    9769753
  • 财政年份:
    2016
  • 资助金额:
    $ 39.63万
  • 项目类别:
NEI CENTER CORE GRANT FOR VISION RESEARCH
NEI 中心视觉研究核心资助
  • 批准号:
    9336307
  • 财政年份:
    2016
  • 资助金额:
    $ 39.63万
  • 项目类别:
NEI Center Core Grant for Vision Research
NEI 中心视觉研究核心资助
  • 批准号:
    10273076
  • 财政年份:
    2016
  • 资助金额:
    $ 39.63万
  • 项目类别:
CORE A - Administrative Core
核心 A - 行政核心
  • 批准号:
    10273077
  • 财政年份:
    2016
  • 资助金额:
    $ 39.63万
  • 项目类别:
NEI Center Core Grant for Vision Research
NEI 中心视觉研究核心资助
  • 批准号:
    10670892
  • 财政年份:
    2016
  • 资助金额:
    $ 39.63万
  • 项目类别:
Role of Retinoic Acid in the Regulation of the Blood-Retinal Barrier.
视黄酸在血视网膜屏障调节中的作用。
  • 批准号:
    9334214
  • 财政年份:
    2016
  • 资助金额:
    $ 39.63万
  • 项目类别:
Role of Retinoic Acid in the Regulation of the Blood-Retinal Barrier.
视黄酸在血视网膜屏障调节中的作用。
  • 批准号:
    10011815
  • 财政年份:
    2016
  • 资助金额:
    $ 39.63万
  • 项目类别:
Cole Eye Institute Vision Science Training Program
科尔眼科研究所视觉科学培训计划
  • 批准号:
    10407662
  • 财政年份:
    2015
  • 资助金额:
    $ 39.63万
  • 项目类别:

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IgG1 抗体的抗原非依赖性血管生成抑制中的性别二态性
  • 批准号:
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