This phase I application hypothesizes that agents inhibiting farnesyltransferase (FT) can suppress ocular neovasculariza- tion (NV). N-[2(S)-[2-(R)-Amino-3-mercaptopropylamno]-3-methylbutyl]- Phe-Met-OH, a known inhibitor of FT, will be tested for its ability to: 1) inhibit subretinal NV in a novel transgenic mouse model in which vascular endothelial growth factor (VEGF) is expressed in retinal photoreceptors and 2) suppress retinal NV in a murine model of oxygen- induced ischemic retinopathy. Feasibility will be demonstrated if maximally tolerated, intraperitoneal (i.p.) doses of the inhibitor cause a statistically significant reduction in NV compared to vehicle- treated controls. Phase II will consist of optimization of the doses and formulation of inhibitors and performance of safety studies. PROPOSED COMMERCIAL APPLICATION: The proposed commercial applications for this grant are the development of drugs that can be used to treat patients with retinal or choroidal neovascularization.
Thesaurus Terms: alkyltransferase, angiogenesis, angiogenesis inhibitor, enzyme inhibitor, nonsurgical revascularization, retina diabetic retinopathy, dosage, drug administration route, macular degeneration, visual photoreceptor laboratory mouse, transgenic animal
