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.
The
for this grant are the development of drugs that can be used to treat patients with retinal or choroidal neovascularization.
| Ueno, Shinji; Pease, Mary Ellen; Wersinger, Delphine M Bonnet et al. (2008) Prolonged blockade of VEGF family members does not cause identifiable damage to retinal neurons or vessels. J Cell Physiol 217:13-22 |
