Postnatal Weight Gain Modifies Severity and Functional Outcome of Oxygen-Induced Proliferative Retinopathy

• DOI: 10.2353/ajpath.2010.100526
• Publication Date: 2010-11-06T01:11:47Z
• Authors: Andreas Stahl; Jing Chen; Przemyslaw Sapieha; Molly R. Seaward; Nathan M. Krah; Roberta J. Dennison; Tara Favazza; Felicitas Bucher; Chatarina Löfqvist; Huy Ong; Ann Hellström; Sylvain Chemtob; James D. Akula; Lois E.H. Smith
• Keywords: Vascular Endothelial Growth Factor A; 2. Zero hunger; Age Factors; Infant, Newborn; Oxygen Inhalation Therapy; Parturition; Prognosis; Weight Gain; Severity of Illness Index; Retina; Mice, Inbred C57BL; Oxygen; Disease Models, Animal; Mice; 03 medical and health sciences; 0302 clinical medicine; Animals, Newborn; Animals; Humans; Retinopathy of Prematurity

In clinical studies, postnatal weight gain is strongly associated with retinopathy of prematurity (ROP). However, animal studies are needed to investigate the pathophysiological mechanisms of how postnatal weight gain affects the severity of ROP. In the present study, we identify nutritional supply as one potent parameter that affects the extent of retinopathy in mice with identical birth weights and the same genetic background. Wild-type pups with poor postnatal nutrition and poor weight gain (PWG) exhibit a remarkably prolonged phase of retinopathy compared to medium weight gain or extensive weight gain pups. A high (r(2) = 0.83) parabolic association between postnatal weight gain and oxygen-induced retinopathy severity is observed, as is a significantly prolonged phase of proliferative retinopathy in PWG pups (20 days) compared with extensive weight gain pups (6 days). The extended retinopathy is concomitant with prolonged overexpression of retinal vascular endothelial growth factor in PWG pups. Importantly, PWG pups show low serum levels of nonfasting glucose, insulin, and insulin-like growth factor-1 as well as high levels of ghrelin in the early postoxygen-induced retinopathy phase, a combination indicative of poor metabolic supply. These differences translate into visual deficits in adult PWG mice, as demonstrated by impaired bipolar and proximal neuronal function. Together, these results provide evidence for a pathophysiological correlation between poor postnatal nutritional supply, slow weight gain, prolonged retinal vascular endothelial growth factor overexpression, protracted retinopathy, and reduced final visual outcome.