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A. Stahl, P. Sapieha, J. Chen, K. L. Willett, R. J. Dennison, N. M. Krah, M. R. Seaward, A. Hellstrom, C. Lofqvist, L. E. H. Smith; Postnatal Weight Gain Determines Severity of Retinopathy in the OIR Mouse Model. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3331.
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The mouse model of oxygen-induced retinopthy (OIR) is one of the most widely used animal models for retinopathy of prematurity (ROP). Clinical studies have found postnatal weight gain to be a strong predictor for the severity of ROP. The aim of our study was to investigate the effect of postnatal weight gain in the OIR mouse retina and identify mechanisms involved in determining the severity of ROP.
Postnatal weight gain was recorded from P7 to P35 in C57BL/6 mice (n = 210). Based on distinct weight gain patterns, three different groups were identified: pups with extensive, normal and poor postnatal weight gain (termed EPG, NPG and PPG). For all three groups, serum levels of IGF-1, glucose and ghrelin were measured at P17; the extent of retinal vessel loss (VO) and neovascularization (NV) was analyzed from P15 to P35 and retinal gene expression was compared using qPCR.
Mice with poor postnatal weight gain (PPG) show delayed and prolonged retinal NV with maximal severity from P19 to P23, mirrored by prolonged VEGF upregulation compared to EPG or NPG pups. Furthermore, regrowth of physiologic vasculature is significantly impaired in PPG pups resulting in persistent VO up to P35. In regard to underlying mechanisms, we found PPG pups to have significantly reduced levels of IGF-1 and non-fasting blood glucose at P17, along with elevated serum ghrelin levels.
Our data confirm the clinical observation of low postnatal weight gain as a predictor of prolonged and more severe ROP. Our results further suggest insufficient metabolic activity (low IGF-1 and/or low glucose) as one of the determining factors. Beyond the clinical implications, the robust effect of postnatal weight gain on VO, NV and vessel regrowth has important implications for all studies performed with the widely-used OIR model. Weight gain over time is a powerful variable in this model and needs to be controlled in order to obtain reliable and consistent OIR results.
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