In Vivo Ocular Angiogenesis Assay

描述（由申请人提供）：在工业化国家，糖尿病视网膜病变（DR）和年龄相关性黄斑变性（AMD）是导致成年人失明的两个主要原因。这两种情况都涉及血管异常、新血管增生和渗漏。早产儿视网膜病变（ROP）是新生儿失明的主要原因，在出生后补充氧气维持早产儿。这种疾病涉及视网膜强烈的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，这通常是由角膜损伤和感染引起的。目前的哺乳动物眼部新生血管模型需要冗长、繁琐的手术操作，而且并不总是能改善视力；另一种用于研究眼部新生血管过程和评估药物效果的快速、微创动物模型将有助于确定新的治疗方法。一期研究利用斑马鱼开发了一种微板法，用于定量血管生成化合物对眼部新生血管的影响。第二阶段的研究将对可用的商业化合物进行试点筛选，并确认在传统动物模型中发现的阳性“命中”。二期研究将进一步验证斑马鱼模型在筛选治疗涉及新生血管的衰弱性疾病的药物方面的效用。通过提供一种定量的体内实验来评估药物对眼部新生血管的影响，提议的斑马鱼实验将促进治疗涉及新生血管的衰弱性疾病的治疗药物的开发。

DESCRIPTION (provided by applicant): Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are the two leading causes of blindness in adults in the industrialized world. Both conditions involve vascular abnormalities, proliferation and leakage of new blood vessels. Retinopathy of prematurity (ROP) is a major cause of newborn blindness in premature infants maintained by oxygen supplementation during the postnatal period. This disease 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 models for ocular neovascularization require lengthy, tedious surgical manipulation and do not always result in improved vision; an alternative rapid, less invasive animal model for studying the process of ocular neovascularization and assessing drug effects will facilitate identification of new therapeutics. Using zebra fish, Phase I research developed a micro plate assay for quantifying effects of angiogenic compounds on ocular neovascularization. Phase II research will perform a pilot screen of available commercially compounds and confirm positive "hits" identified in conventional animal models. Phase II research will further validate the utility of the zebra fish model for screening drugs for treating debilitating diseases involving neovascularization. By providing a quantitative in vivo assay for assessing drug effects on ocular neovascularization, the proposed zebra fish assay will facilitate development of therapeutic drugs for treating debilitating diseases involving neovascularization.