Regulation of ocular angiogenesis by microRNAs

microRNA对眼部血管生成的调节

• 批准号: 8531950
• 负责人: Shusheng Wang
• 金额: $ 35.74万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8531950
• 关键词: Age related macular degeneration; Angiogenic Factor; Blood Vessels; Choroid; Choroidal Neovascularization; Data; Development; Diabetic Retinopathy; Disease; Endothelial Cells; Endothelium; Exudative age-related macular degeneration; Eye Development; Fibroblast Growth Factor; Future; Gene Expression; Gene Targeting; Genetic; Goals; Lasers; MAP Kinase Gene; MicroRNAs; Mitogen-Activated Protein Kinases; Modeling; Outcome; Pathogenesis; Pathologic Neovascularization; Pathway interactions; Pattern; Play; Proto-Oncogene Proteins c-akt; Regulation; Retina; Retinal; Retinal Diseases; Retinopathy of Prematurity; Role; Signal Transduction; Solutions; Stress; Technology; Testing; Therapeutic; Vascular Diseases; Vascular Endothelial Growth Factors; Vascular Endothelium; angiogenesis; in vivo; mouse model; neovascularization; ocular angiogenesis; response; retinal angiogenesis; small molecule; therapeutic target; transcription factor

DESCRIPTION (provided by applicant): This project focuses on microRNA mechanisms on ocular angiogenesis. Angiogenesis plays a central role in eye development and also many major blinding retinal diseases, such as age related macular degeneration (AMD).The discovery of MicroRNAs as small endogenous RNAs regulating gene expression post-transcriptionally has revolutionized our understanding of genetic pathway networks, and ignited tremendous studies to explore microRNA therapeutics for numerous diseases. Our broad long-term goals are: (a) to understand the mechanisms of how specific microRNAs regulate ocular vascular development and (b) to decipher the roles of these microRNAs in vascular retinopathies. Our recent studies show that a specific microRNA, miR-126, is an endothelial cell specific microRNA regulating angiogenic pathways in response to vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). We also have preliminary data that miR-126 is expressed specifically in the endothelium in the retina/choroid, and is required for sprouting retinal angiogenesis. Our organizing hypothesis for this proposal is that by regulating multiple angiogenic pathways miR-126 plays a critical regulatory role in ocular angiogenesis and in the pathogenesis of neovascular AMD. As a small molecule with multiple regulatory functions, miR-126 would be an attractive therapeutic target for blinding vascular retinopathies. Specific Aim I is to define the expression pattern and regulation mechanism of miR-126 in the retina/choroid. Specific Aim II is to identify the requirement and mechanism whereby miR-126 regulates retinal vascular development. Specific Aim III is to determine the mechanism by which miR-126 regulates neovascularization in a laser induced choroidal neovascularization model.

描述（由申请人提供）：该项目的重点是关于眼血管生成的microRNA机制。血管生成在眼睛发育中起着核心作用，也起着许多主要的视网膜疾病，例如与年龄相关的黄斑变性（AMD）。在转录后调节基因表达的小型内源性RNA的发现，发现了遗传途径网络的理解，并引发了巨大的研究，以探索Microdorna疗法的巨大研究。我们的广泛长期目标是：（a）了解特定microRNA如何调节眼血管发育的机制以及（b）破译这些microRNA在血管视网膜病变中的作用。我们最近的研究表明，特定的microRNA miR-126是一种内皮细胞特异性微洋纳，可响应血管内皮生长因子（VEGF）和成纤维细胞生长因子（FGF），调节血管生成途径。我们还拥有初步数据，即miR-126在视网膜/脉络膜的内皮中特别表达，并且是发芽视网膜血管生成所必需的。我们对该提案的组织假设是，通过调节多个血管生成途径，miR-126在眼血管生成和新生血管AMD的发病机理中起关键的调节作用。作为具有多种调节功能的小分子，miR-126将是盲目的血管视网膜病变的有吸引力的治疗靶标。具体目的是定义视网膜/脉络膜中miR-126的表达模式和调节机制。具体目标II是确定miR-126调节视网膜血管发育的需求和机制。具体目的III是确定miR-126在激光诱导的脉络膜新生血管形成模型中调节新血管形成的机制。