Regulation of Ocular Angiogenesis by microRNAs

microRNA 调控眼部血管生成

基本信息

批准号：
10202608
负责人：
Shusheng Wang
金额：
$ 36.86万
依托单位：
TULANE UNIVERSITY OF LOUISIANA
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10202608
关键词：
Actins Age related macular degeneration Cells Choroidal Neovascularization Complex Data Development Disease Epithelial Fibroblasts Fibrosis Genetic Goals Human Inflammation Lasers Lead MADH2 gene Mesenchymal MicroRNAs Modeling Nonexudative age-related macular degeneration Pathogenesis Pathologic Neovascularization Pathologic Processes Pathway interactions Patients Pharmaceutical Preparations Phosphorylation Process Recurrence Regulation Retinal Dystrophy Role Signal Transduction Stimulus Structure of retinal pigment epithelium Technology Testing Therapeutic Transforming Growth Factor beta Transgenic Mice Untranslated RNA Vascular Endothelial Growth Factors angiogenesis base bevacizumab cell type cofilin combat depolymerization epithelial to mesenchymal transition extracellular geographic atrophy macrophage mouse model neovascularization ocular angiogenesis ocular neovascularization polymerization response rho small molecule sodium iodate therapeutic miRNA

项目摘要

Anti-VEGF therapy is the current mainstay for treating wet age-related macular degeneration (AMD). The efficacy of anti-VEGF therapy is still limited, and some patients failed to respond to the treatment. No drug is currently available for subretinal fibrosis associated with AMD. Therefore, there is a great need for developing alternative or superior approaches to the current anti-VEGF therapy to combat choroidal neovascularization (CNV) and subretinal fibrosis in AMD. Epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells can lead to fibrosis. However, the contribution of RPE EMT in AMD pathogenesis remains undefined. MicroRNAs belong to a large group of noncoding RNAs which can regulate diverse pathways in different cell types. The involvement of miRNAs in CNV, RPE EMT and fibrosis remains unclear. This project focuses on elucidating the function and mechanism of miRNAs in the context of complex pathological processes involved in AMD, including CNV, EMT of the RPE cells and fibrosis. The contribution of EMT of RPE cells in AMD mouse models will be examined by genetic lineage tracing. The organizing hypothesis of the proposal is that a single miRNA, miR-24, can repress CNV, EMT of RPEs and fibrosis, therefore representing an excellent “one drug/multiple targets” model for treating AMD. In addition, the contribution of EMT of RPE cells in AMD pathogenesis will also be established. Aim I is to define the function of miR-24 in ocular neovascularization, inflammation and fibrosis. Aim II is to determine the role of miR-24-regulated EMT and fibrosis of RPE cells.

抗VEGF治疗是目前治疗湿性年龄相关性黄斑的主要疗法抗VEGF治疗的疗效仍然有限，部分患者失败。目前尚无药物可用于治疗与视网膜下纤维化相关的疾病。因此，非常需要开发替代或更好的方法来替代 AMD。目前抗 VEGF 疗法可对抗脉络膜新生血管 (CNV) 和视网膜下纤维化 AMD 中视网膜色素上皮 (RPE) 细胞的上皮间质转化 (EMT) 可以然而，RPE EMT 在 AMD 发病机制中的作用仍然存在。未定义 MicroRNA 属于一大类非编码 RNA，可以调节多种。不同细胞类型中 miRNA 参与 CNV、RPE EMT 和纤维化的途径。该项目的重点是阐明 miRNA 的功能和机制。 AMD 涉及的复杂病理过程的背景，包括 CNV、EMT RPE 细胞和纤维化。AMD 小鼠模型中 RPE 细胞 EMT 的贡献将是该提案的组织假设是单一的。 miRNA、miR-24 可以抑制 CNV、RPE 的 EMT 和纤维化，因此代表了一种治疗AMD的优秀“一药多靶点”模式此外，EMT的贡献。 RPE 细胞在 AMD 发病机制中的作用也将得到确定。目标 I 是确定 RPE 细胞的功能。目的II是确定miR-24在眼部新生血管形成、炎症和纤维化中的作用。 miR-24 调节 RPE 细胞的 EMT 和纤维化。