Ibuprofen improves oxygen-induced retinopathy in a mouse model

Abstract

Purpose. Retinopathy of prematurity is a developmental vascular anomaly occurring in the incompletely vascularized retina of the premature infant. Ibuprofen is a nonsteroidal anti-inflammatory agent similar to indomethacin, but with less pronounced side-effects. The goal of the study was to test the hypothesis that ibuprofen would improve oxygen-induced retinopathy in a mouse model. Methods. C57BL6 mice pups were exposed to 75% oxygen from postnatal day 7 through postnatal day 12. Ibuprofen was administered along with oxygen exposure as a single subcutaneous dose of 40 mg/kg/day for 5 days. Animals were sacrificed on postnatal day 17 through postnatal day 20. The severity of retinopathy was assessed by a retinopathy scoring system of fluorescein- conjugated dextran-perfused retinal flat mounts and by quantitation of extra-retinal nuclei by use of periodic acid-Schiff-stained retinal sections. Results. Animals that received ibuprofen during hyperoxia exposure had a significantly lower median (25th, 75th quartile) retinopathy score of 6 (5, 7.5) compared with animals that received oxygen only, with a score of 12 (10.5, 12.5), with p < 0.005. Animals given ibuprofen during hyperoxia exposure had a significantly lower extra-retinal nuclei count per section (14.2 ± 3.6) compared with animals that were only exposed to oxygen (26.8 ± 5.8), with p < 0.005. Ibuprofen did not affect the growth of the animals. Conclusion. Ibuprofen improves oxygen-induced retinopathy when administered concurrently with the injury phase without affecting the normal retinal development of the animals.