Treatment of Ocular Neovascularization by Inhibitors

抑制剂治疗眼部新生血管

• 批准号: 6878477
• 负责人: PETER LOUIS GEHLBACH
• 金额: $ 22.44万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6878477
• 关键词: amacrine cells; angiogenesis; angiogenesis inhibitors; angiostatins; enzyme linked immunosorbent assay; fluorescence microscopy; gene expression; genetically modified animals; immunocytochemistry; laboratory mouse; light microscopy; nonhuman therapy evaluation; pathologic process; polymerase chain reaction; retinal ganglion; retinal pigment epithelium; southern blotting; transfection /expression vector; transforming growth factors; uvea disorder; vascular endothelial growth factors; visual photoreceptor

DESCRIPTION: (Applicant's Abstract) Retinal and choroidal neovascularization (NV) account for a large majority of severe visual loss in developed countries each year and therefore new treatments are needed. Angiostatin and endostatin are proteolytic fragments of larger proteins that have been shown to inhibit tumor angiogenesis in mice. Pigment epithelium-derived factor (PEDF) is produced by the retinal pigmented epithelium (RPE) and other cells of the eye and inhibits corneal NV. Transforming growth factor-b I (TGFP 1) has been demonstrated to inhibit blood vessel growth in some settings. We hypothesize that expression of angiostatin, endostatin, PEDF and/or TGFP 1 in the eye will inhibit retinal and/or choroidal NV. To test this hypothesis, I will express each of these proteins in transgenic mice and compare transgene-positive mice with littermate controls in 3 models of ocular NV. I will perform similar experiments using mice that have had intraocular injection of adenovirus (AV) or adeno-associated virus (AAV) vector containing a construct for one of the 4 proteins, an approach with direct clinical application. Research training will focus on gaining a detailed understanding of the pathogenesis of ocular NV under Peter Campochiaro at the Wilmer Institute and the molecular biology of AAV under William Hauswirth at the University of Florida. Clinical training will focus on subretinal surgery utilizing techniques that will be used for gene transfer to the retina and RPE in humans. This project should provide important new information, while providing me the training necessary to become an independent investigator in the area of ocular NV utilizing a gene therapy approach. It will also provide me with clinical training to eventually translate the knowledge into new treatments for patients.

描述：（申请人摘要）视网膜和脉络膜新生血管