Young Ossabaw Pigs Fed a Western Diet Exhibit Early Signs of Diabetic Retinopathy. Invest Ophthalmol Vis Sci 2018 May 01;59(6):2325-2338
Date
05/31/2018Pubmed ID
29847637Pubmed Central ID
PMC5937800DOI
10.1167/iovs.17-23616Scopus ID
2-s2.0-85046700624 (requires institutional sign-in at Scopus site) 16 CitationsAbstract
PURPOSE: Recent 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.
METHODS: Four-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.
RESULTS: Young 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.
CONCLUSIONS: This 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.
Author List
Lim RR, Grant DG, Olver TD, Padilla J, Czajkowski AM, Schnurbusch TR, Mohan RR, Hainsworth DP, Walters EM, Chaurasia SSAuthor
Shyam S. Chaurasia PhD Associate Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBasement Membrane
Diabetes Mellitus, Experimental
Diabetic Retinopathy
Diet, Western
Female
Follow-Up Studies
Male
Microscopy, Electron
Retina
Swine
Swine, Miniature
Time Factors
