Dexamethasone reduces oxygen induced retinopathy in a mouse model.
Dexamethasone is widely used in the postnatal period. Its impact on retinopathy of prematurity (ROP) is extremely controversial; published studies have found a detrimental, protective, or no effect on ROP. The goal of this study was to test the hypothesis that use of dexamethasone during the injury phase (oxygen exposure) reduces the severity of oxygen-induced retinopathy (OIR) in a mouse model. C57BL6 mice pups were exposed to either room air or hyperoxia (75% FiO2) from postnatal d 7 through 12 (PN7-12) with or without dexamethasone (0.5 mg/kg/d s.c.) and killed on PN17-21. Retinopathy was assessed by a scoring system of retinal flat mount preparations and periodic acid-Schiff (PAS) staining of retinal sections. Pups exposed to dexamethasone and oxygen had a lower median retinopathy score of 5 (4, 6) [median (25th, 75th quartile)] compared with animals exposed to oxygen alone with median score of 9 (6, 10) with p < 0.001. PAS staining for extra retinal neovascularization in the dexamethasone and oxygen treated animals showed a significant reduction in number of nuclei extending beyond the inner limiting membrane when compared with oxygen exposed alone (p = 0.04). Animals treated with dexamethasone had decreased weight gain compared with control animals. Dexamethasone did not appear to affect the normal development of retinal vasculature as assessed by the scoring system when compared with control animals. Thus, dexamethasone decreases severity of OIR without having an adverse effect on normal retinal vascular development in the mouse model. We speculate that dexamethasone decreases the injury response that occurs during the hyperoxic phase, thus protecting the developing vasculature and improving the subsequent retinopathy.
Department of Pediatrics, Georgetown University Medical Center, Washington, DC 20007, USA.
T
T
Rotschild
B N
BN
Nandgaonkar
K
K
Yu
R D
RD
Higgins
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D018496:Hyperoxia; D007231:Infant, Newborn; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D010100:Oxygen / Q000633:toxicity*; D012160:Retina / Q000187:drug effects / Q000473:pathology*; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology*; D012178:Retinopathy of Prematurity / Q000473:pathology / Q000517:prevention & control*
D003907:Dexamethasone; D010100:Oxygen