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I. Y. Benador, G. T. Berry, A. B. Fulton, T. L. Favazza, R. M. Hansen, J. D. Akula; Maternal Antioxidant Supplementation in Oxygen-Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4472.
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Oxidative stress in retinal neurons plays a key role in the retinopathy of prematurity (ROP) disease process (Fulton, 2009). Injection of antioxidants (AOs) reduces the severity of vasculopathy (Penn, 1997) and improves electroretinographic (ERG) outcomes (Dorfman, 2006). Since ROP disproportionally impacts developing countries, antioxidants delivered through the pregnant or nursing mother might be a viable approach to neurovascular protection in ROP.
A cocktail of 12 AO molecules, selected to target multiple stages of reactive oxygen species generation, was blended with an AIN93G chow at concentrations of 1 and 15%; a control chow (CC) was also studied. The 1% chow (1%C) was designed to mimic in a rat dam a dose 10× to 100× RDA (or typical intake) of each AO in human; the 15% chow (15%C) was allometrically scaled to the rat. All diets were isocholoric. The diversity of AOs increased the likelihood of some passing the several biological barriers between a mother’s digestive tract and a nursing infant’s retina. The chows were fed to pregnant Sprague-Dawley dams at gestational day 19 through the course of the study. Each diet was fed to a litter of Penn et al. (1995) "50/10 model" rats (ROP rats) and room-air-reared controls (RAR rats). Rod photoreceptor and post-receptor retinal function was derived from ERG records collected on P19±1. Following ERG, one retina was flatmounted for quantification of avascular retina (AR) and clockhours of neovascularization (CHNV), and the other lysed for Western blot analysis of the oxidative stress markers heme oxygenase 1 (HO-1) and C/EBP-homologous protein (CHOP). Data were analyzed by ANOVA.
Higher doses of AO resulted in decreased CHNV. There was significantly less AR in 1%C-ROP rats than in CC- or 15%C-ROP rats. However, 15%C was severely toxic in both ROP and RAR rats; every ERG parameter in 15%C-rats was significantly compromised. ERG parameters were nearly always slightly (but not significantly) better in 1%C-ROP rats than CC-ROP rats, and no 1%C-RAR rat ERG parameter was significantly worse than in CC-RAR rats. Significant increases in CHOP and HO-1 levels were detected in 1%C-ROP rats relative to CC-fed animals.
The 1% chow showed beneficial effect to retinal vascular coverage and no harm to function. Elevated levels of HO-1 are consistent with an enhanced response to the oxygen insult, but higher levels of CHOP indicate ER stress. An optimized maternal AO regimen might provide greater benefit.
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