New Model for Eye Disease

描述（由申请人提供）：视网膜疾病，无论是遗传决定的还是继发于全身性疾病，是工业化世界失明的主要原因。超过530万美国人患有糖尿病视网膜病变。另有160万60岁以上的美国人患有老年性黄斑变性。早产儿视网膜病变是早产儿失明的一个主要原因，在产后期间通过补充氧气维持。利用基因敲低技术，该SBIR旨在验证斑马鱼胚胎作为由血管缺陷引起的人类眼部疾病的完整动物模型。这种SBIR将表征胚胎发生和模式，以及斑马鱼眼睛血管系统的形成。斑马鱼是眼部血管疾病的良好动物模型。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快速发育，因此可以很容易地对其进行检测和药物治疗。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。此外，早期胚胎正常发育不需要血液，通过扩散获得足够的氧气。这允许进行基因敲低实验，这将导致哺乳动物模型的早期致死。

DESCRIPTION (provided by applicant): Diseases of the retina, either genetically determined or secondary to systemic disease, are the leading cause of blindness in the industrialized world. More than 5.3 million Americans are affected by diabetic retinopathy. Another 1.6 million Americans over age 60 have age-related macular degeneration. Retinopathy of prematurity is a major cause of blindness in premature infants maintained by oxygen supplementation during the postnatal period. Using gene knockdown technology, this SBIR aims to validate the zebrafish embryo as a whole animal model for human eye diseases that result from vascular defects. This SBIR will characterize embryogenesis and patterning, and the formation of the vasculature of the zebrafish eye. Zebrafish is a good animal model for eye vascular disease. Orthologs of many genes involved in angiogenesis in mammals have been identified in zebrafish. Assays and drug treatment can easily be 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. Furthermore, early stage embryos do not require blood for normal development, obtaining sufficient oxygen by diffusion. This permits performance of gene knockdown experiments, which would result in early lethality in mammalian models.