Glial, neuronal, vascular, RPE and inflammatory cell damage in a new Western diet-induced primate model of diabetic retinopathy.

This study investigated retinal changes in a Western diet (WD)-induced non-human primate (NHP) model of Type 2 diabetes (T2D). Rhesus NHP aged 15-17 years old were fed a high fat diet (n=7) for more than 5 years with the aim of reflecting the traditional WD. Age-matched controls (n=6) were fed a standard laboratory primate diet. Retinal fundus, OCT, autofluorescence imaging and fluorescein angiography were undertaken prior to euthanasia. To assess diabetic retinopathy, eyes were examined using trypsin digests, lipofuscin autofluorescence and multi-marker immunofluorescence on cross sections and wholemounts. Retinal imaging showed venous engorgement and tortuosity, aneurysms, macular exudates, dot and blot hemorrhages, and a marked increase in fundus autofluorescence. Post-mortem changes included: decreased cluster of differentiation marker 31 (CD31) blood vessel density (p < 0.05); increased acellular capillaries (p < 0.05); increased density of ionized calcium binding adaptor molecule (Iba-1) expressing amoeboid microglia/macrophage ; loss of regular distribution in stratum and spacing typical of ramified microglia; increased immunoreactivity of aquaporin (AQP) 4 and glial fibrillary acidic protein (GFAP) (p<0.05). Rhodopsin immunoreactivity (p < 0.05) in rods and NeuN+ neuronal density of 50% (p < 0.05); however, were decreased. This is the first report of a primate model of DR solely induced by a Western Diet (WD) and that replicates key features of human DR.