Rat Model of Type 2 Diabetes Mellitus Recapitulates Human Disease in the Anterior Segment of the Eye

Changes in the anterior segment due to type 2 diabetes mellitus (T2DM) are not well characterized, in part due to the lack of a reliable animal model. This study evaluates changes in the anterior segment, including crystalline lens health, corneal endothelial cell density, aqueous humor metabolites and ciliary body vasculature, in a rat model of type 2 diabetes mellitus (T2DM) compared with human eyes. Sprague-Dawley male rats were fed a high fat diet (HFD, 45% fat) or normal diet, and HFD rats were injected intraperitoneally with streptozotocin (STZ) to create a model of T2DM. Microscopic analysis was performed to determine cataract formation and corneal endothelial cell density. Metabolomics of rat aqueous humor was performed to determine diabetes-related aqueous alterations. Transmission electron microscopy was used to assess qualitative ultrastructural changes of diabetic rat and human ciliary process microvessels at the site of aqueous formation. Diabetic rats demonstrated cataracts, lower corneal endothelial cell densities, altered aqueous metabolites, and ciliary body ultrastructural changes including vascular endothelial cell activation, pericyte degeneration, perivascular edema, and basement membrane reduplication. These findings recapitulated diabetic changes in human eyes. Results support use of this model for studying ocular manifestations of T2DM and support a hypothesis postulating blood-aqueous barrier breakdown and vascular leakage at the ciliary body as a mechanism for diabetic anterior segment pathology.