Development of a Rabbit Model of Retinal Vascular Permeability to Evaluate the Inhibitory Effects of Soluble VEGF Receptor 2 and Soluble Neuropilin-1

Abstract

Abstract: : Purpose: Vascular endothelial growth factor (VEGF) is a specific and potent mitogen for vascular endothelial cells and has been shown to cause ocular and retinal edema. We sought to develop a rabbit model of retinal edema by injecting VEGF into the vitreal cavity. This model was then employed to test the ability of soluble Kinase Domain Receptor (sKDR) and soluble Neuropilin-1 (sNRP1), to alter VEGF-mediated vascular hyperpermeability. Methods: We injected VEGF protein at varying concentrations (0.0625 µg, 0.3125 µg and 1.25 µg) into the vitreous cavity of New Zealand Red rabbits on experimental days 1 and 5. Fluorescein angiography was performed on days 3 and 8. Four rabbits received either 1) 8.5x10⁷ particles of recombinant replication defective sKDR lentivirus, 2) 8.5x10⁷ particles of replication defective sNRP1 lentivirus, or 3) a combined dosage of 4.25 x10⁷ particles of sKDR lentivirus and 4.25 x10⁷ particles of sNRP-1 lentivirus. The contralateral eyes served as a control with PBS or no injection. . Results: Retinal edema along with retinal hemorrhages was seen in the rabbits with 1.25 µg of VEGF protein injected into the intravitreal cavity by day 8. No retinal edema was seen in the eyes where 0.0625 µg or 0.3125 µg VEGF protein was injected in the intravitreal cavity. Analysis of the effects of the intravitreal injection of lentviral vectors is currently underway. Conclusions: Injection of VEGF into the vitreous cavity of rabbits results in a reproducible alteration of retinal vascular permeability and retinal edema. This model of edema may prove a useful tool in the elucidation of the pathophysiology of retinal edema and as a target for therapeutic modalities.

Keywords: retina • gene transfer/gene therapy • diabetes