Young Ossabaw Pigs Fed a Western Diet Exhibit Early Signs of Diabetic Retinopathy

Abstract

PurposeRecent clinical data suggest an increasing prevalence of obesity and type 2 diabetes in adolescents, placing them at high risk of developing diabetic retinopathy during adult working years. The present study was designed to characterize the early retinal and microvascular alterations in young Ossabaw pigs fed a Western diet, described as a model of metabolic syndrome genetically predisposed to type 2 diabetes.MethodsFour-month-old Ossabaw miniature pigs were divided into two groups, lean and diet-induced obesity. Obese pigs were fed a Western diet with high-fat/high-fructose corn syrup/high-choleric content for 10 weeks. Blood and retina were collected for biochemical profiling, trypsin digest, flatmounts, Fluoro-Jade C staining, electron microscopy, quantitative PCR, immunohistochemistry, and Western blots.ResultsYoung Ossabaw pigs had elevated fasting blood glucose after feeding on a Western diet for 10 weeks. Their retina showed disrupted cellular architecture across neural layers, with numerous large vacuoles seen in cell bodies of the inner nuclear layer. Microvessels in the obese animals exhibited thickened basement membrane, along with pericyte ghosts and acellular capillaries. The pericyte to endothelial ratio decreased significantly. Retina flatmounts from obese pigs displayed reduced capillary density, numerous terminal capillary loops, and string vessels, which stained collagen IV but not isolectin IB4. Quantitative PCR and Western blots showed significantly high levels of basement membrane proteins collagen IV and fibronectin in obese pigs.ConclusionsThis is the first study to describe the ultrastructural neuronal and vascular changes in the retina of young Ossabaw pigs fed a Western diet, simulating early signs of diabetic retinopathy pathogenesis.

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