Indomethacin improves oxygen-induced retinopathy in the mouse

Retinopathy of prematurity is a disease commonly affecting extremely premature babies. Indomethacin is widely used in the perinatal period. The goal of the present study was to test-the hypothesis that indomethacin will improve retinopathy in a mouse model when administered during the period of injury (hyperoxia exposure) to the developing retinal vasculature. C57BL6 mice pups were exposed to 75% oxygen from postnatal d 7 through 12. Indomethacin was administered along with the oxygen exposure as a single subcutaneous dose of 0.5 mg/kg/d for 5 d. Animals were killed on postnatal d 17 through 20. The severity of retinopathy was assessed by a retinopathy scoring system of fluorescein-conjugated dextran-perfused retinal flat mounts and by quantitation of extraretinal nuclei by use of periodic acid-Schiff-stained retinal sections. Animals that received indomethacin during hyperoxia exposure had a significantly lower median (25th, 75th quartile) retinopathy score 5 (4.5, 6) compared with animals that received oxygen [8 (7.5, 10)]. Animals given indomethacin during hyperoxia exposure had a significantly lower extraretinal nuclei count per section(13.3 +/- 4.6) (mean +/- SD) Compared with animals that were oxygen exposed (41.9 +/- 14.7). Indomethacin did not affect the normal development of the retinal vasculature or the growth of the animals. The data show that indomethacin improves oxygen-induced retinopathy when administered concurrently with the injury phase without affecting the normal retinal development or growth of the animals.