| 1 |
Article Gene therapy for ocular neovascularization: a cure in sight. 2003
Reich SJ, Bennett J. · FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, The University of Pennsylvania, 310 Stellar Chance Labs, 422 Curie Blvd, Philadelphia, Pennsylvania 19104-6069, USA. · Curr Opin Genet Dev. · Pubmed #12787796 No free full text.
Abstract: Recent advances in the field of ocular gene transfer have led researchers pursuing treatment for age-related macular degeneration and diabetic retinopathy to turn to gene therapy for the answer. Viral vector-mediated delivery of both anti-angiogenic proteins and molecules that inhibit the eye's endogenous pro-angiogenic factors has successfully diminished the pathology of ocular diseases in rodent models. A gene-therapy solution to the debilitating blindness caused by ocular neovascularization may be on the horizon.
|
| 2 |
Retraction Intravitreal injection of vascular endothelial growth factor small interfering RNA inhibits growth and leakage in a nonhuman primate, laser-induced model of choroidal neovascularization. 2004
Tolentino MJ, Brucker AJ, Fosnot J, Ying GS, Wu IH, Malik G, Wan S, Reich SJ. · Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, 51 North 39th Street, Philadelphia, PA 19104, USA. · Retina. · Pubmed #15076954 No free full text.
Abstract: PURPOSE: To determine the safety and efficacy of small interfering RNA (siRNA) directed against vascular endothelial growth factor (VEGF) in a nonhuman primate model of laser-induced choroidal neovascularization (CNV). METHODS: Each animal received laser rupture of Bruch's membrane to induce CNV in both eyes. Each animal was then randomized to receive 0.05 mL of either vehicle alone or VEGF siRNA at 70 microg, 150 microg, or 350 microg in both eyes by intravitreal injection. Eyes were monitored weekly by ophthalmic examination, color photography, and fluorescein angiography for 36 days after laser injury. Electroretinograms were measured at baseline and at 5 weeks after laser. CNV on fluorescein angiograms were measured for area and graded for clinically significant leakage in a standardized, randomized, and double-masked fashion on days 15, 22, 29, and 36 after laser. RESULTS: VEGF siRNA did not cause any change in electroretinographic, hemorrhage, inflammation, or clinical signs of toxicity. A single administration of VEGF siRNA significantly inhibited growth of CNV and attenuated angiographic leakage in a dose-dependent manner. CONCLUSION: Intravitreal injection of VEGF siRNA is capable of inhibiting the growth and vascular permeability of laser-induced CNV in a nonhuman primate in a dose-dependent manner. This study demonstrates preclinical proof of a principle that supports proceeding to clinical studies of VEGF siRNA in patients with exudative age-related macular degeneration.
|