Effects of Subconjunctival Injection of Anti-Vascular Endothelial Growth Factor Antibody on Oxygen-Induced Ischemic Retinopathy in a Neonatal Rat Model

Abstract

The present study investigated the effects of subconjunctival injections of an anti-rat vascular endothelial growth factor (anti-VEGF) antibody on oxygen-induced retinopathy (OIR) in a neonatal rat model. OIR was induced by daily cycles of 80% oxygen (20.5h), room air (0.5h), and a progressive return to 80% oxygen (3h) for 12 days [until postnatal day (P) 12]. On P12, rats received subconjunctival injections in their right eye of 0.1 or 1.0μg anti-VEGF antibody (or 1.0μg goat IgG as a control). No injections were made into the left eye. On P18, rats were killed and their retinas were removed and flat-mounted before being stained with adenosine diphosphatase. Retinal neovascularization (NV) was scored and the extent of avascular areas, as a percentage of total retinal area (%AVA), was determined using image analysis. Although there was a tendency for lower mean NV scores in eyes injected with 0.1 and 1.0μg anti-VEGF compared with control (4.3±1.1, 2.3±1.0, and 6.7±1.3, respectively; n=10–13), the difference failed to reach statistical significance. Similarly, although there was a tendency for mean %AVA to be lower in the injected eyes for both the 0.1 and 1.0μg anti-VEGF groups compared with control (15±3%, 13±3%, and 25±4%, respectively; n=10–13), the differences were not significant. Similar tendencies were observed in the contralateral eyes. Although further studies using larger numbers of rats are needed to obtain statistically significant results, the results of the present study suggest that the subconjunctival injection of anti-VEGF antibody may prove to be a useful route of administration in conjunction with intravitreal injections, which are the generally used method at present. However, careful attention should be paid to the possibility of systemic side effects.