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Julie Mocko, Yanhong Wei, Laura Frishman, Xanthi Couroucli; Effects of vitamin A on a rat model of retinopathy of prematurity (ROP). Invest. Ophthalmol. Vis. Sci. 2013;54(15):5079.
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ROP is a leading cause of preventable childhood visual impairment and blindness. This hypoxic ischemic disease, caused by prematurity and high oxygen (O2) therapy, disrupts vascular development and leads to neural retinal injury, pathologic neovascularization, scar formation and risk of retinal detachment. Current treatment involves ablation of avascular peripheral retina, with sacrifice of peripheral vision, or intraocular anti-VEGF injections with unknown effects to other organs. Vitamin (vit) A and its metabolites play a role in the metabolically demanding visual cycle, and they have antioxidant and neuroprotective properties. Therefore, in this study we tested the hypothesis that treatment of newborn rats with vitamin A prevents oxygen mediated retinopathy and abnormal neovascularization.
ROP was induced in albino Fisher 344 rat pups by placing them in an environment of 95% O2 from postnatal day (P) 1 to P7 and then returning them to room air. Control pups were raised in room air. Pups received intraperitoneal injections of either vehicle (corn oil; 20 ml/kg), or vit A (2mg/kg) from P1 to P5. Dark-adapted electroretinograms (ERGs) were recorded for age points: P20-22, P25-27, P34-36, and P80+. Stimulus-response functions were compared using repeated measures ANOVA, and two-way ANOVA to compare parameters of fitted hyperbolic functions. After recording, retinal flatmounts were analyzed for vascular coverage and neovascularization. One-way ANOVA was used to compare vascular measures.
Animals exposed to O2 and given corn oil showed significant postreceptoral dysfunction for ages P20-22 and P25-27, with negative ERGs and no b-waves (p<0.05). These animals also showed neovascularization and incomplete retinal vascular coverage. At these same ages, animals exposed to O2 and given vit A showed some preservation of inner retinal function, as reflected by b-wave amplitudes no different from controls. These animals also exhibited preservation of vascular development, with more complete vascular coverage and almost no neovascularization. By P34-37 although functional abnormalities began resolving, vascular coverage lagged behind controls. By P80+, all groups showed similar ERGs and vascular coverage.
Vitamin A given during early postnatal O2 exposure can have a protective effect on neural and vascular development of retinas with ROP.
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