Hypoxia Induced Ocular Neovascularization Model

缺氧诱导眼部新生血管模型

• 批准号: 6786541
• 负责人: WEN L SENG
• 金额: $ 17.27万
• 依托单位: PHYLONIX PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6786541
• 关键词: angiogenesis; disease /disorder model; drug screening /evaluation; embryo /fetus; embryogenesis; eye circulation; eye pharmacology; gene expression; hypoxia; immunocytochemistry; in situ hybridization; model design /development; polymerase chain reaction; technology /technique development; zebrafish

DESCRIPTION (provided by applicant) The leading cause of blindness in adults is diabetic retinopathy and age-related macular degeneration. Both conditions involve vascular abnormalities, leakage and proliferation of new blood vessels. Retinopathy of prematurity is a major cause of newborn blindness in premature infants maintained by oxygen supplementation during the postnatal period. This condition involves intense neovascularization of the retina and leads to retinal detachment. Another cause of blindness is corneal neovascularization, which often results from injury and infection in the cornea. Current mammalian ocular neovascularization models for screening potential therapeutics require tedious surgical manipulation and are lengthy. Using zebrafish embryos, this SBIR proposes to develop a hypoxia induced zebrafish ocular neovascularization model. Zebrafish is a good animal model for eye disease. Orthologs of many genes involved in angiogenesis in mammals have been identified in zebrafish. Assays and drug treatment are easily performed on the zebrafish embryo because of its rapid ex-utero development. Embryos are transparent, permitting visual observation of defects in development and angiogenesis in the eye and elsewhere. This SBIR will characterize embryogenesis and patterning, and blood vessel formation in the zebrafish eye. This SBIR will also confirm expression of hypoxia-induced genes in zebrafish. The zebrafish model will facilitate screening and development of therapeutics for eye diseases.

描述（由申请人提供） 成人失明的主要原因是糖尿病性视网膜病变和年龄相关性黄斑变性。这两种情况都涉及血管异常、渗漏和新血管增殖。早产儿视网膜病变是导致产后靠吸氧维持的早产儿新生儿失明的主要原因。这种情况涉及视网膜的强烈新生血管形成并导致视网膜脱离。失明的另一个原因是角膜新生血管形成，这通常是由角膜损伤和感染引起的。目前用于筛选潜在治疗方法的哺乳动物眼部新生血管模型需要繁琐的手术操作并且时间较长。该 SBIR 提议使用斑马鱼胚胎开发缺氧诱导的斑马鱼眼部新生血管模型。斑马鱼是眼部疾病的良好动物模型。已在斑马鱼中鉴定出许多参与哺乳动物血管生成的基因的直向同源物。由于斑马鱼胚胎在子宫外发育迅速，因此很容易对其进行测定和药物治疗。胚胎是透明的，可以目视观察眼睛和其他部位的发育缺陷和血管生成。该 SBIR 将表征斑马鱼眼睛中的胚胎发生和模式以及血管形成。该 SBIR 还将证实斑马鱼缺氧诱导基因的表达。斑马鱼模型将有助于眼部疾病治疗方法的筛选和开发。