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. ? ?
