Young Ossabaw Pigs Fed a Western Diet Exhibit Early Signsof Diabetic Retinopathy

Investigative Ophthalmology & Visual Science

article

Rayne R. Lim¹  DeAna G. Grant⁴  T. Dylan Olver²  Jaume Padilla⁵  Alana M. Czajkowski⁸  Teagan R. Schnurbusch⁸  Rajiv R. Mohan¹  Dean P. Hainsworth⁹  Eric M. Walters⁸  Shyam S. Chaurasia¹ 

[1] Ocular Immunology and Angiogenesis Lab, Department of Veterinary Medicine & Surgery, University of Missouri;Department of Biomedical Sciences, University of Missouri;Harry S. Truman Memorial Veteran Hospital;Electron Microscopy Core, University of Missouri;Department of Nutrition and Exercise Physiology, University of Missouri;Dalton Cardiovascular Research Center, University of Missouri;Child Health, University of Missouri;National Swine Resource and Research Center, University of Missouri;Mason Eye Institute, University of Missouri

关键词: diabetic retinopathy;    Ossabaw pig;    type 2 diabetes;    microvasculature;    basementmembrane;   

DOI  :  10.1167/iovs.17-23616

学科分类：社会科学、人文和艺术（综合）

来源: Association for Research in Vision and Ophthalmology

【 摘 要 】

PURPOSE. Recent clinical data suggest an increasing prevalence of obesity and type 2 diabetesin adolescents, placing them at high risk of developing diabetic retinopathy during adultworking years. The present study was designed to characterize the early retinal andmicrovascular alterations in young Ossabaw pigs fed a Western diet, described as a model ofmetabolic syndrome genetically predisposed to type 2 diabetes.METHODS. Four-month-old Ossabaw miniature pigs were divided into two groups, lean anddiet-induced obesity. Obese pigs were fed a Western diet with high-fat/high-fructose cornsyrup/high-choleric content for 10 weeks. Blood and retina were collected for biochemicalprofiling, trypsin digest, flatmounts, Fluoro-Jade C staining, electron microscopy, quantitativePCR, immunohistochemistry, and Western blots.RESULTS. Young Ossabaw pigs had elevated fasting blood glucose after feeding on a Westerndiet 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 inthe obese animals exhibited thickened basement membrane, along with pericyte ghosts andacellular capillaries. The pericyte to endothelial ratio decreased significantly. Retinaflatmounts from obese pigs displayed reduced capillary density, numerous terminal capillaryloops, and string vessels, which stained collagen IV but not isolectin IB4. Quantitative PCRand Western blots showed significantly high levels of basement membrane proteins collagenIV and fibronectin in obese pigs.CONCLUSIONS. This is the first study to describe the ultrastructural neuronal and vascularchanges in the retina of young Ossabaw pigs fed a Western diet, simulating early signs ofdiabetic retinopathy pathogenesis.

【 授权许可】

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