Role of RPE-derived VEGF in Choroid Development and Stability

RPE 衍生的 VEGF 在脉络膜发育和稳定性中的作用

基本信息

  • 批准号:
    7060810
  • 负责人:
  • 金额:
    $ 43.06万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2004
  • 资助国家:
    美国
  • 起止时间:
    2004-05-01 至 2008-04-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Although a significant body of evidence indicates a role for the retinal pigment epithelium in the development and maintenance of the choroidal vasculature, the mechanisms that underlie this relationship are unknown. In addition to an important function in the normal retina, the interactions between RPE and the choroidal vasculature are central to a number of retinal pathologies, including age-related macular diseases (ARMD) such as geographic atrophy. Several findings point to a possible role for vascular endothelial growth factor (VEGF) as a mediator of the RPE cell survival effect on choroidai vessels. Data from experimental models indicate a survival function for VEGF in vessel stabilization, RPE in the adult make VEGF, and choroidal endothelial cells express VEGF receptors, which we show are constitutively activated in the adult. We therefore propose to test the hypothesis that RPE-derived VEGF is necessary for the development and maintenance of the choroidal vasculature by the following aims. (1) To determine the expression pattern of VEGF family members and their receptors (VEGFR1, VEGFR2, VEGFR3, and the neuropilins), and VEGF receptor activation status in the choroid-RPE complex during development and in the adult. (2) To examine the role of VEGF in choroidal vascular development using mice that express only VEGF188, an isoform not normally made by RPE, and mice with an RPE-specific deletion of VEGF. The role of VEGF in the maintenance of the adult choroidal vasculature will be determined by inhibition of the VEGFR2 tyrosine phosphorylation using SU5416, a small molecule VEGFR2-selective tyrosine kinase inhibitor; and interference with the interaction between RPE-derived VEGF and choroidal endothelial VEGFR2 using an inducible DN-VEGFR2 transgenic mouse model. (3) To assess the ability of exogenously added VEGF to "rescue" choroidal loss due to experimentally induced RPE destruction. RPE will be destroyed by systemic administration of sodium iodate (NalO3) and the role of VEGF in trophic effects of RPE on the choroid will be assessed by investigating the ability of exogenously added VEGF to rescue the choroidal loss. Results of these studies will provide mechanistic insight into the means by which RPE support normal choroidal function, and thus may reveal targets for therapeutic intervention into the blinding diseases of macular degeneration.
描述(由申请人提供):尽管大量证据表明视网膜色素上皮细胞在脉络膜血管系统的发育和维持中发挥作用,但这种关系的机制尚不清楚。除了在正常视网膜中的重要功能之外,RPE和脉络膜血管系统之间的相互作用对于许多视网膜病理学是重要的,包括年龄相关性黄斑疾病(ARMD),例如地图状萎缩。一些发现指出血管内皮生长因子(VEGF)作为脉络膜血管上RPE细胞存活效应的介体的可能作用。来自实验模型的数据表明VEGF在血管稳定中的存活功能,成人中的RPE产生VEGF,并且脉络膜内皮细胞表达VEGF受体,我们显示其在成人中组成性激活。因此,我们建议通过以下目的来检验RPE衍生的VEGF对于脉络膜血管系统的发育和维持是必要的这一假设。(1)确定VEGF家族成员及其受体(VEGFR 1、VEGFR 2、VEGFR 3和神经纤毛蛋白)的表达模式,以及发育期间和成人脉络膜-RPE复合体中VEGF受体的激活状态。(2)使用仅表达VEGF 188(一种通常不由RPE产生的同种型)的小鼠和RPE特异性VEGF缺失的小鼠,研究VEGF在脉络膜血管发育中的作用。VEGF在维持成人脉络膜脉管系统中的作用将通过使用SU 5416(一种小分子VEGFR 2选择性酪氨酸激酶抑制剂)抑制VEGFR 2酪氨酸磷酸化;和使用诱导型DN-VEGFR 2转基因小鼠模型干扰RPE衍生的VEGF和脉络膜内皮VEGFR 2之间的相互作用来确定。(3)评估外源性添加VEGF“拯救”实验诱导的RPE破坏所致脉络膜丧失的能力。通过全身施用碘酸钠(NaIO 3)来破坏RPE,并且通过研究外源性添加的VEGF挽救脉络膜损失的能力来评估VEGF在RPE对脉络膜的营养作用中的作用。这些研究的结果将为RPE支持正常脉络膜功能的手段提供机制性见解,从而可能揭示黄斑变性致盲疾病的治疗干预靶点。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Patricia Ann D'Amore其他文献

Patricia Ann D'Amore的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Patricia Ann D'Amore', 18)}}的其他基金

Investigation of endomucin as a novel regulator of angiogenesis
内粘蛋白作为血管生成的新型调节剂的研究
  • 批准号:
    9414681
  • 财政年份:
    2017
  • 资助金额:
    $ 43.06万
  • 项目类别:
Investigation of endomucin as a novel regulator of angiogenesis
内粘蛋白作为血管生成的新型调节剂的研究
  • 批准号:
    10219259
  • 财政年份:
    2017
  • 资助金额:
    $ 43.06万
  • 项目类别:
Investigation of endomucin as a novel regulator of angiogenesis
内粘蛋白作为血管生成的新型调节剂的研究
  • 批准号:
    10456724
  • 财政年份:
    2017
  • 资助金额:
    $ 43.06万
  • 项目类别:
Investigation of endomucin as a novel regulator of angiogenesis
内粘蛋白作为血管生成的新型调节剂的研究
  • 批准号:
    9238401
  • 财政年份:
    2017
  • 资助金额:
    $ 43.06万
  • 项目类别:
Fourth Biennial AMD Symposium
第四届AMD双年研讨会
  • 批准号:
    9193821
  • 财政年份:
    2016
  • 资助金额:
    $ 43.06万
  • 项目类别:
Third Biennial Symposium on Age Related Macular Degeneration
第三届年龄相关性黄斑变性双年研讨会
  • 批准号:
    8783667
  • 财政年份:
    2014
  • 资助金额:
    $ 43.06万
  • 项目类别:
Transmission Electron Microscope
透射电子显微镜
  • 批准号:
    8052990
  • 财政年份:
    2011
  • 资助金额:
    $ 43.06万
  • 项目类别:
Mechanisms That Mediate The Absence of Lymphatics in the Retina
调节视网膜淋巴管缺失的机制
  • 批准号:
    7458430
  • 财政年份:
    2008
  • 资助金额:
    $ 43.06万
  • 项目类别:
Mechanisms That Mediate The Absence of Lymphatics in the Retina
调节视网膜淋巴管缺失的机制
  • 批准号:
    7618416
  • 财政年份:
    2008
  • 资助金额:
    $ 43.06万
  • 项目类别:
Role of RPE-derived VEGF in Choroid Development and Stability
RPE 衍生的 VEGF 在脉络膜发育和稳定性中的作用
  • 批准号:
    8019446
  • 财政年份:
    2004
  • 资助金额:
    $ 43.06万
  • 项目类别:

相似海外基金

Nonlocal Variational Problems from Physical and Biological Models
物理和生物模型的非局部变分问题
  • 批准号:
    2306962
  • 财政年份:
    2023
  • 资助金额:
    $ 43.06万
  • 项目类别:
    Standard Grant
Point-of-care optical spectroscopy platform and novel ratio-metric algorithms for rapid and systematic functional characterization of biological models in vivo
即时光学光谱平台和新颖的比率度量算法,可快速、系统地表征体内生物模型的功能
  • 批准号:
    10655174
  • 财政年份:
    2023
  • 资助金额:
    $ 43.06万
  • 项目类别:
Multi-scale stochastic systems motivated by biological models
由生物模型驱动的多尺度随机系统
  • 批准号:
    RGPIN-2015-06573
  • 财政年份:
    2022
  • 资助金额:
    $ 43.06万
  • 项目类别:
    Discovery Grants Program - Individual
Micro-electrofluidic platforms for monitoring 3D human biological models
用于监测 3D 人体生物模型的微电流体平台
  • 批准号:
    DP220102872
  • 财政年份:
    2022
  • 资助金额:
    $ 43.06万
  • 项目类别:
    Discovery Projects
Multi-scale stochastic systems motivated by biological models
由生物模型驱动的多尺度随机系统
  • 批准号:
    RGPIN-2015-06573
  • 财政年份:
    2021
  • 资助金额:
    $ 43.06万
  • 项目类别:
    Discovery Grants Program - Individual
Multi-scale stochastic systems motivated by biological models
由生物模型驱动的多尺度随机系统
  • 批准号:
    RGPIN-2015-06573
  • 财政年份:
    2020
  • 资助金额:
    $ 43.06万
  • 项目类别:
    Discovery Grants Program - Individual
Harnessing machine learning and cloud computing to test biological models of the role of white matter in human learning
利用机器学习和云计算来测试白质在人类学习中的作用的生物模型
  • 批准号:
    2004877
  • 财政年份:
    2020
  • 资助金额:
    $ 43.06万
  • 项目类别:
    Fellowship Award
A Portable low-cost, Point of Investigation CapCell Scope to Image and Quantify the Major Axes of Metabolism and the Associated Vasculature in In vitro and In vivo Biological Models
便携式低成本调查点 CapCell 示波器,用于对体外和体内生物模型中的主要代谢轴和相关脉管系统进行成像和量化
  • 批准号:
    9899988
  • 财政年份:
    2019
  • 资助金额:
    $ 43.06万
  • 项目类别:
Multi-scale stochastic systems motivated by biological models
由生物模型驱动的多尺度随机系统
  • 批准号:
    RGPIN-2015-06573
  • 财政年份:
    2019
  • 资助金额:
    $ 43.06万
  • 项目类别:
    Discovery Grants Program - Individual
A Portable low-cost, Point of Investigation CapCell Scope to Image and Quantify the Major Axes of Metabolism and the Associated Vasculature in In vitro and In vivo Biological Models
便携式低成本调查点 CapCell 示波器,用于对体外和体内生物模型中的主要代谢轴和相关脉管系统进行成像和量化
  • 批准号:
    9753458
  • 财政年份:
    2019
  • 资助金额:
    $ 43.06万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了