Intraocular expression of endostatin reduces VEGF-induced retinal vascular permeability, neovascularization, and retinal detachment.

SPECIFIC AIMSVascular endothelial growth factor (VEGF) causes several pathologic changes in the retina. Each of these abnormalities, including vascular leakage leading to macular edema, neovascularization, and retinal detachment, are seen in patients with diabetic retinopathy. The major goal of our study was to determine whether intraocular expression of endostatin by gene transfer prevents VEGF-induced pathologies in the retina.PRINCIPAL FINDINGS1. Inducible, long-term intraocular expression of endostatin is feasibleFor most studies, a bovine immunodeficiency viral vector (BIVendostatin) was used to achieve intraocular expression of endostatin because it provides long-term expression with no identifiable toxicity. In addition, we tested a pair of gutless adenoviral vectors designed to provide tamoxifen-inducible expression of endostatin (InduceAGVendostatin). Mice given a subretinal injection of InduceAGVendostatin showed intense immunostaining for endostatin throughout the retina when given tamoxifen, b...