Retinal capillary basement membrane thickening in a porcine model of diabetes mellitus

Purpose: Current animal models of diabetic microangiopathy, including diabetic retinopathy (DR), have substantial limitations. To determine whether the diabetic pig would provide an improved large animal model of DR, a 20-week porcine model of diabetic dyslipidemia that manifests appreciable macrovasculopathy was evaluated for development of retinal microvascular changes associated with diabetes mellitus (hereafter referred to as diabetes) in humans. Methods: The effect of diabetes alone or in combination with high dietary fat intake on retinal capillary morphology was assessed. Cell density in the retinal capillaries was evaluated by use of elastase digestion isolation of the retinal vascular bed, and retinal capillary basement membrane thickness was determined by use of electron microscopic analyses. Results: Diabetic pigs fed a normal diet had significantly (P < 0.001) thicker retinal capillary basement membranes than did nondiabetic animals. High fat intake did not contribute to basement membrane thickening. Significant effects of diabetes or diet on retinal capillary cell densities were not observed, nor did diabetes induce formation of microaneurysms typical of advanced diabetic retinopathy. Conclusions: The rapid development of retinal capillary basement membrane thickening in diabetic pigs makes this animal model useful for early intervention and mechanistic studies for this diabetes-associated microvascular change.