Effect of indomethacin on the incidence and severity of neovascularization in a rat model of retinopathy of prematurity

Purpose. Indomethacin has been reported to inhibit angiogenesis in several animal models. We investigated the effect of systemic indomethacin on neovascularization in a rat model for retinopathy of prematurity (ROP). Methods. 50 newborn Sprague-Dawley rats were exposed to 7 days of 80% O₂ followed by 5 days on room air. Once during each of the first 7 days, inspired O₂ was reduced to 10% for 30 mins and returned to 80% O₂ over 3hrs. 26 of the rats were randomly assigned to receive indomethacin (5mg/kg/d subcutaneously for 12 days) and 24 to receive vehicle control. All rats were sacrificed on day 13 after intracardiac injection of fluorescein under deep anesthesia. The retinas were dissected and flat mounted for ADPase staining and fluorescent microscopy. The presence and number of clock hours of abnormal neovascularization were evaluated in a masked manner and the ratios of vascularized:total retinal area were calculated using computer assisted image analysis. Chi-square and ANOVA were used for analysis. Results. Neovascularization occurred in 53% of rats receiving indomethacin vs. 37% control (p=0.4). The severity of neovascularization was similar in rats receiving indomethacin and control (1.6 clock hrs ± 2.1 SD vs. 1.5 ± 2.7, p=0.9). The ratio of vascularized:total retinal area was similar in rats receiving indomethacin and control (82 ± 6% vs 82 ± 9%, p = 0.9). Conclusions. Systemic indomethacin did not decrease the incidence or severity of abnormal neovascularization in this rat model of ROP. Our results suggest that, in contrast to other corneal and retinal models, neovascularization in this model is not mediated by prostaglandins that are inhibited by systemic indomethacin.