Pathological Features of Diabetic Retinopathy in Spontaneously Diabetic Torii Fatty Rats

Abstract

Purpose : The Spontaneously Diabetic Torii (SDT) fatty rat, established by introducing the fa allele (obesity gene) of the Zucker fatty rat into the SDT rat genome, is a new model of obese type 2 diabetes. We studied the pathologic features of diabetic retinopathy (DR) in this animal.

Methods : The eyes were enucleated in SDT fatty, SDT (controls), and SD (Sprague Dawley) rats (normal controls) at 8, 16, 24, 32, and 40 weeks of age (n=5-6 for each rat type at each age). The retinal thickness and number of retinal folds were evaluated. The mean retinal thicknesses were measured 500, 1,000, and 1,500 microns from the optic nerve disc. The numbers of retinal folds, defined as deformation from the outer nuclear layer to photoreceptor layer, were measured within 1,500 microns of the optic nerve disc. Immunostaining for glial fibrillary acidic protein (GFAP) and vascular endothelial growth factor (VEGF) was performed. Quantitative analyses of the immunopositive regions were performed using the Hybrid Cell Count Module (Keyence, Tokyo, Japan).

Results : At 24 weeks, the mean retinal thicknesses 500 microns from the optic nerve disc in SDT fatty rats, SDT fatty rats, and SD rats, respectively, were 244.5±16.4, 239.3±42.9 microns, and 165.0±7.9 microns (SDT fatty vs SDT, P=0.52). No retinal folds were seen in SD rats. The peaks of retinal folds were noted at 32 weeks of age in SDT rats (1.2±0.8) and those at 24 weeks of age in SDT fatty rats (2.8±1.2) （SDT fatty vs SDT: P＜0.01）(Fig). At 40 weeks, the respective mean area ratios of GFAP positivity in the specimens were 8.0±1.9%, 5.7±1.8%, and 4.3±1.6% (SDT fatty vs SDT, P<0.01). At 40 weeks, the respective mean area ratios of VEGF positivity in the specimens were 8.2±4.7%, 4.0±1.2%, and 1.5±0.7% (SDT fatty vs SDT, P<0.05).

Conclusions : The retinas tended to be thicker in SDT fatty and SDT rats than in SD rats. Retinal folds in SDT fatty rats developed earlier and were more severe than in SDT rats. Quantitative analysis showed that the GFAP- and VEGF-positive regions in retinas of SDT fatty rats were significantly larger than in SDT rats. SDT fatty rats developed more severe DR earlier than the SDT rats. SDT fatty rats might be useful as a type 2 diabetes animal model to study DR.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.