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FRANCOIS BRIAND, SOPHIE ANTONELLI, Virginie Mauro, Nicolas Cimbolini, Masami Shinohara, Emmanuel Brousseau, Takeshi Ohta, Yasushi Kageyama, Laurence Feraille, Thierry Sulpice; The Uni-Nephrectomized SDT Fatty Rat, a novel Type 2 diabetic model of Diabetic Nephropathy, develops features of diabetic retinopathy over 10 weeks. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3573.
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Animal models of spontaneous diabetes are still needed to mimic human diabetic retinopathy. We recently developed a novel model of diabetic nephropathy using the uni-nephrectomized Spontaneously Diabetic Torii (SDT) fatty rat. Fed a salt rich diet, this hypertensive/obese/type 2 diabetic rat develops advanced renal glomerulosclerosis, inflammation and fibrosis, and a >50% glomerular filtration rate decline within 10 weeks. Here we investigated whether this rat model would also develop features of diabetic retinopathy.
Two groups of 6-week old, male, Sprague Dawley (SD, control) rats and SDT fatty rats (n=10 per group) underwent unilateral nephrectomy. After a 1-week recovery period, rats were fed for 10 weeks a chow diet with 0.3% salt in drinking water (i.e. from 7 weeks to 17 weeks of age). Diabetic retinopathy was evaluated in terms of i) retinal function by electroretinogram and oscillatory potentials, ii) integrity of blood-retinal barrier by albumin–Evans blue complex leakage, iii) microscopy histopathologic studies by glial fibrillary acidic protein IHC.
One week after nephrectomy, SDT fatty rats showed a diabetic phenotype, with elevated blood glucose levels (597 ± 13 vs. 120 ± 3 mg/dL in control rats, p<0.001) that sustained to 17 weeks of age. Ocular examination indicated no lens opacity in control rats, but a progressive mild to severe cataract in SDT fatty rats between 12 and 17 weeks of age. Retinal neurologic dysfunction began at 12 weeks of age in SDT fatty rat: compared to control rats, A- and B-wave amplitudes during standard scotopic ERG recording were significantly reduced, with significant peak delay in implicit times of oscillatory potentials. At the 17th week of age, Müller cells activation (measured by GFAP immunostaining) was increased in SDT fatty rats as compared to control, indicating reactive gliosis in retina. Evans blue retinal flat-mount of uni-nephrectomized SDT fatty rat also showed vessel dilatation and tortuosity at the 17th week of age without any evidence of retinal vascular permeability.
Uni-nephrectomized SDT fatty rats develop features of diabetic retinopathy in parallel with diabetic nephropathy. Our original data set suggests that this rat model is suitable to evaluate the effects of drugs on these type 2 diabetes co-morbidities.
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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