Reduction of basement membrane thickening in diabetic cat retina by sulindac

Capillary basement membrane thickening is one of the earliest histologic lesions in diabetic retinopathy. Its pathogenesis is not understood; however, recent evidence suggests that aldose reductase may play a role. In this study, a new animal model, the diabetic cat, was used to determine whether retinal capillary basement membrane thickening occurred early in the course of hyperglycemia, and if so, whether it could be inhibited by sulindac, an aldose reductase inhibitor. Retinal capillary basement membrane thickness was significantly increased in diabetic cats compared to normal cats (114 +/- 15 vs 72 +/- 12 nm, mean +/- SD) [corrected]. Basement membrane thickness was significantly less in sulindac-treated diabetic cats (93 +/- 9 nm) compared to the untreated diabetic cats (114 +/- 15 nm). In addition, quantitation of endothelial cells, pericytes, and contacts between endothelial cells and pericytes in electron micrographs revealed that they were not reduced in number in untreated diabetic cats compared to normal or sulindac-treated diabetic animals.