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Molly R. Seaward, Andreas Stahl, Jing Chen, Mike Sapieha, Nathan M. Kran, Aimee M. Juan, Colman J. Hatton, Tara Favazza, James D. Akula, Lois E. Smith; Postnatal Weight Gain Modifies Severity and Functional Outcome of Oxygen-Induced Proliferative Retinopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3167.
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The mouse model of oxygen-induced retinopathy (OIR) is a commonly-used animal model for retinopathy of prematurity (ROP). Clinical studies have found postnatal weight gain to be a strong indicator for the severity of ROP. Our study investigates the effects of postnatal weight gain on the severity of ROP in the OIR mouse retina and the molecular mechanisms involved.
Postnatal weight gain was recorded from P7 to P35 in C57BL/6 mice (n = 210). Three groups were classified by three distinct postnatal weight gain patterns: extensive, normal and poor postnatal weight gain (termed EWG, NWG and PWG). Retinal vessel loss (VO) and neovascularization (NV) were analyzed from P15 to P35. Serum levels of IGF-1, glucose and ghrelin were measured at P17. Retinal function in adult EWG and PWG mice was assessed with electroretinograms (ERGs) at P70.
Mice with poor postnatal weight gain (PWG) show significantly delayed and prolonged retinal NV compared with NWG or EWG pups, through P17 and peaking at P19-21. This is in association with prolonged VEGF upregulation, reduced serum IGF-1 and fasting blood glucose levels and increased serum ghrelin levels. Retinopathy resolution is slow in PWG pups and is not reached until P35. At P70 ERGs show a remarkable impairment in visual function in PWG pups with significantly lower responses for all six parameters compared to EWG pups, without morphologic differences in retinal vascularization.
Our data provide evidence for a pathophysiological correlation between poor postnatal weight gain and extended retinopathy, suggesting insufficient metabolic activity as a potential determining factor. These data confirm the clinical observation of low postnatal weight gain as a predictor of prolonged and more severe ROP.
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