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Julie A Mocko-Strand, Yanhong Wei, Laura J Frishman, Deborah C Otteson, Xanthi I Couroucli; Effects of high dose vitamin A supplementation on retinal thickness in a rat model of oxygen induced retinopathy (OIR).. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3387.
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© ARVO (1962-2015); The Authors (2016-present)
Prematurity and high oxygen (O2) therapy disrupt retinal vascular development by decreasing expression of pro-angiogenic factors, such as vascular endothelial growth factor A (Vegf-A), leading to retinal hypoxia, neural retinal injury, and neovascularization. Our previous work showed that high dose vitamin A (HDVA) supplementation preserved retinal vascular development, down-regulated anti-angiogenic pigment epithelial derived factor (Pedf), prevented sustained up-regulation of Vegf-A, and preserved inner retinal function in a hyperoxic rat model of OIR. This study investigates if HDVA-mediated improvements in retinal function are associated with a rescue of retinal thickness in this model.
OIR was induced in albino Fisher 344 rats by exposure to 95-100% O2 from postnatal day 1 (P1) to P7, then returned to room air. Controls were raised in room air (Air). All pups received daily intraperitoneal injections of either vehicle alone (Veh, corn oil, 33ml/kg), or with HDVA (2mg/kg) from P1 to P5. At P21 and P35, eyes were fixed, embedded in glycol methacrylate, sectioned (5μm thickness), and stained with 1% toludine blue. Digital images (40x, ≥200μm apart) captured near the optic nerve head (central) and the ora serrata (peripheral) were analyzed (ONL to ILM) using a custom MATLAB program. Statistical analysis used one-way analysis of variance, with post-hoc Tukey’s HSD.
Retinas of Veh+Air rats were thicker centrally (237μm) vs. peripherally (175μm, p<0.001); HDVA+Air rats showed a similar trend (226μm vs. 192μm, p=0.068). In OIR, total retinal thickness was 32% thinner centrally (161μm, p<0.03) than Air controls, but did not differ between Veh and HDVA. There were no differences in central vs. peripheral retinal thickness in Veh or HDVA treated OIR rats. Both Veh and HDVA treated OIR rats had significant thinning of inner retinal layers (INL to ILM), both centrally (p<0.01) and peripherally (p<0.04) vs. Air controls, with the INL and IPL most affected. Outer retinal thickness (ONL, OPL) did not differ significantly across all groups.
Although HDVA rescued inner retinal function in this rat model of OIR, it did not prevent hyperoxia-induced inner retinal thinning. The rescue of retinal function by HDVA may be due to amelioration of retinal hypoxia by promoting retinal vascular development through modulation of genes involved in angiogenesis.
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