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Shyam S Chaurasia, Rayne Lim, Dylan Olver, Jaume Padilla, Rajiv R Mohan, Eric Walters, Dean P Hainsworth; A Novel Miniature Porcine Model for the Early-Onset of Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3587.
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Human clinical studies suggest that early-onset type 2 diabetes (T2DM) results in a more aggressive form of diabetic retinopathy (DR). We sought to establish an early-onset translational large animal model for DR using young Ossabaw mini pigs.
Four-months old Ossabaw mini pigs were fed normal chow (lean) or a western diet with high-fat/high-fructose corn syrup/high-choleric content (obese) for 10 weeks. Blood was collected for biochemical profiling and retina was processed for trypsin digest, flat mounts, electron microscopy (EM), qPCR, immunohistochemistry and western blots.
Ossabaw mini pigs became obese after 10 weeks of western diet and demonstrated elevated fasting blood glucose levels and hyperlipidemia. Harvested pig retinas 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 had thickened basement membrane along with pericyte ghosts and acellular capillaries. Furthermore, Pericyte-to-endothelial ratio was found significantly decreased. Retina flat mounts of pig retinas displayed reduced capillary density, numerous terminal capillary loops stained with collagen IV but not isolectin-IB4. qPCR and western blots showed significantly high levels of basement membrane proteins-collagen IV and fibronectin.
This is the first study to describe the ultrastructural neuronal and vascular changes in the retina of young Ossabaw mini pigs fed a western diet simulating early-onset of DR pathology.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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