Ibuprofen improves oxygen-induced retinopathy in a mouse model.
OBJECTIVE
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.


CONCLUSIONS
Ibuprofen improves oxygen-induced retinopathy when administered concurrently with the injury phase without affecting the normal retinal development of the animals.
Sharma
Jotishna
J
Department of Pediatrics, Division of Neonatology, Georgetown University Children's Medical Center, Washington, DC, USA.
Barr
Sybil M
SM
Geng
Yixun
Y
Yun
Yan
Y
Higgins
Rosemary D
RD
D000818:Animals; D000831:Animals, Newborn; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003911:Dextrans; D004195:Disease Models, Animal; D005260:Female; D005452:Fluoresceins; D006801:Humans; D018496:Hyperoxia / Q000150:complications; D007052:Ibuprofen / Q000627:therapeutic use*; D007231:Infant, Newborn; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000633:toxicity; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D015861:Retinal Neovascularization / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology; D012178:Retinopathy of Prematurity / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003911:Dextrans; D005452:Fluoresceins; C052526:fluorescein-dextran; D010100:Oxygen; D007052:Ibuprofen