The Nile Rat as a Pre-clinical Model for Diabetic Retinopathy

Diabetic retinopathy is the most common microvascular complication of diabetes and a major cause of blindness, but an understanding of the pathogenesis of the disease has been hampered by a lack of accurate animal models. Here we explore the dynamics of retinal cellular changes in the Nile rat (Arvicanthis Niloticus), a carbohydrate-sensitive model for type 2 diabetes. Prior to 37 weeks of diabetes, diabetic Nile rats exhibited increased acellular capillaries and loss of pericytes that correlated linearly with the duration of diabetes. These vascular changes occurred in the presence of microglial infiltration but in the absence of retinal ganglion cell loss. After a prolonged duration of diabetes, the Nile rat exhibits a spectrum of retinal lesions commonly seen in the human condition including vascular leakage, capillary non-perfusion and neovascularization. Our longitudinal study documents a range and progression of retinal lesions in the diabetic Nile rat remarkably similar to those observed in human diabetic retinopathy, and suggests that this model will be valuable in identifying therapeutic strategies.