A Method for Inducing Subretinal Neovascularization in the Rabbit

Abstract

Abstract: : Purpose: To develop a rabbit model of subretinal neovascularization in order to facilitate the study of anti–angiogenesis and anti–proliferative therapies for ocular disease. Methods: Trans–pars–plana injections were performed in the right eyes of Dutch pigmented rabbits. 30 microliters of Matrigel with or without vascular endothelial growth factor were injected into the subretinal space. Phosphate–buffered saline was used as a control. Fundus photography, fluorescein angiography and optical coherence tomography were performed at 1, 2, 4, or 8 weeks. Histologic analysis was performed after sacrifice at these time points with preservation of the eyes in 10% formalin followed by paraffin sectioning and H+E staining. Results: Twenty eyes underwent subretinal Matrigel injection. In all cases, the area of the subretinal Matrigel bleb showed mild pigmentary changes. All treated eyes had angiographic leakage within this localized area at 1 week post–op. The amount of leakage usually increased at weeks 2 and 4 and in some cases persisted at 8 weeks of follow–up. Control eyes showed no leakage at any time point. Optical coherence tomography of treated eyes showed subretinal fluid and a lesion, possibly vascular or fibrotic, at the site of the leakage. Histologic analysis confirmed the presence of new blood vessels beneath the retina in the areas of angiographic leakage. Inflammatory cells were also present within and beneath the retina in these areas. Conclusions: Localized subretinal neovascularization develops in a reproducible fashion after injection of Matrigel into the subretinal space. This method may prove a useful tool for the evaluation of therapies intended to reduce or prevent the growth of choroidal neovascularization.

Keywords: choroid: neovascularization • age–related macular degeneration