In Vivo Ocular Angiogenesis Assay

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Eye diseases related to neovascularization are: diabetic retinopathy and age-related macular degeneration, the two leading causes of adult blindness in developed countries; retinopathy of prematurity, the major cause of vision loss in premature infants; and corneal neovascularization due to corneal injury, infection, or failed transplantation. Using zebrafish, this SBIR aims to develop a quantitative in vivo assay for assessing drug effects on ocular neovascularization. This SBIR will also investigate embryogenesis and patterning. Zebrafish is uniquely suitable for screening drugs that block ocular neovascularization. The pattern of vessels on the surface of the zebrafish eye is tightly regulated, permitting easy visual screening for drug effects. The transparency of the embryo permits identification of defects in vessel development in the eye and throughout the embryo. Rapid ex-utero development of the zebrafish allows drug administration, either by direct incubation in fish water (for small molecule) or injection (for large molecules such as RNA, DNA, morpholinos oligonucleotides, or antibodies). Zebrafish embryos do not require blood for normal development during the first week, obtaining sufficient oxygen by diffusion. Therefore, it is possible to perform treatment of the whole animal with anti-angiogenic drugs. The proposed zebrafish assay will facilitate development of therapeutic drugs to treat eye diseases caused by neoangiogenesis.