Increased angiogenic factors associated with peripheral avascular retina and intravitreous neovascularization: a model of retinopathy of prematurity.

OBJECTIVES To determine expression of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor, and their respective receptors in retinas using a model of retinopathy of prematurity. METHODS Retinas isolated from a 50/10 oxygen (inspired oxygen cycled between 50% oxygen and 10% oxygen every 24 hours)-induced rat model of retinopathy of prematurity (50/10 OIR model), and from room air-raised rat pups (RA) at birth, age 14 days (persistent peripheral avascular retina in the 50/10 OIR model and complete retinal vascularization in RA) and age 18 days (intravitreous neovascularization in the 50/10 OIR model) were analyzed for messenger RNA of VEGF(164), neuropilin 1, neuropilin 2, VEGF receptor 1, VEGF receptor 2, pigment epithelium-derived factor, and pigment epithelium-derived factor receptor by real-time polymerase chain reaction. RESULTS In the 50/10 OIR model compared with RA, fold changes in expression of VEGF(164), neuropilin 1, and neuropilin 2 were significantly increased at ages 14 and 18 days. A trend for increased fold change was noted in expression of VEGF receptor 2 at age 14 days and a significant increase at age 18 days in the 50/10 OIR model compared with RA. Pigment epithelium-derived factor receptor was significantly increased at age 14 days in the 50/10 OIR model compared with RA. CONCLUSION Increased expression of VEGF(164) and angiogenic receptors were found in association with both avascular retina at day 14 and intravitreous neovascularization at day 18 in a relevant model of retinopathy of prematurity. CLINICAL RELEVANCE Increased VEGF and angiogenic receptors may have a role in the development of peripheral avascular retina and stage 3 retinopathy of prematurity.