Abstract
Purpose :
The Vascular Endothelial Growth Factor (VEGF) challenge model first developed by Edelman et. al.1, is routinely used in the rabbit to evaluate the potential of therapies for ocular diseases such as neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Compared to the rabbit, the minipig is a useful species for evaluating intravitreal ocular therapies due to the size, fluid dynamics, and vasculature of the minipig eye. We have developed an experimental VEGF challenge model for use in the Yucatan minipig to evaluate the effect of anti neovascularization therapies on the retina/choroid.
Methods :
Yucatan minipigs were injected IVT with a dose range of VEGF165. Fluorescein angiography (FA) was used to image the retinal vasculature, and a clinical scoring system was developed to quantify retinal vasculopathy at several timepoints post VEGF challenge. Placebo polymer implants and an Avastin positive control were utilized to assess viability of the model.
Results :
An optimal amount of VEGF165 was determined that induces significant leakage in the miniature swine, with the ability to induce leakage for up to 5 days post VEGF challenge. The positive control Avastin was able to inhibit the VEGF165 induced leakage, while the negative control placebo polymeric implants did not protect against retinal vasculature leakage.
Conclusions :
The VEGF challenge model commonly utilized in rabbits can be adapted for use in the Yucatan minipig, a species with more relevant ocular anatomy to humans.
1. Edelman, J.L. Lutz, D., Castro, M.R. Corticosteroids inhibit VEGF-induced vascular leakage in a rabbit model of blood-retinal and blood-aqueous barrier breakdown. Experimental Eye Research, 2005, (80) 249-258.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.