Hypoxia Induced Ocular Neovascularization Model

成人失明的主要原因是糖尿病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、新血管渗漏和增生。早产儿视网膜病变是新生儿失明的主要原因，早产儿在出生后通过补充氧气维持失明。这种情况包括强烈的视网膜新生血管并导致视网膜脱离。失明的另一个原因是角膜新生血管，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，而且时间长。本研究拟利用斑马鱼胚胎建立缺氧诱导的斑马鱼眼部新生血管模型。斑马鱼是眼病的良好动物模型。在斑马鱼中发现了许多与哺乳动物血管生成有关的基因的同源物。由于斑马鱼胚胎在体外的快速发育，化验和药物治疗很容易进行。胚胎是透明的，允许在眼睛和其他地方的发育和血管生成缺陷的视觉观察。这种SBIR将表征胚胎发生和模式，以及斑马鱼眼睛中的血管形成。该SBIR也将证实缺氧诱导基因在斑马鱼中的表达。斑马鱼模型将促进眼病治疗方法的筛选和开发。

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.