Remodeling of Retinal Capillaries in the Diabetic Hypertensive Rat

To document the effect of sustained systemic hypertension on the integrity and ultrastructural morphology of retinal capillaries in diabetic and nondiabetic rats. Normotensive (strain Wistar-Kyoto; WKY) and genetically hypertensive (spontaneously hypertensive; SHR) rats were rendered diabetic by intravenous streptozotocin injection. At 20 weeks of diabetes, endothelial cells, pericytes, and extracellular matrix were evaluated by ultrastructural morphometry. Serum albumin was localized by immunofluorescence microscopy. The endothelial cell layer was markedly thinner in the diabetic normotensive animals. The number of intercellular junctions was reduced in both the nondiabetic and diabetic hypertensive group but less so in the diabetic normotensive group. No significant endothelial cell loss was noted in either of the experimental groups, whereas the number of pericytes and the number of their cytoplasmic processes were reduced in diabetic and hypertensive animals. Significant thickening of the basement membrane and increased permeability to serum albumin were observed in diabetic and hypertensive rats and were strongly enhanced in the combined diseases. Endothelial thinning and shape changes from an elaborate to a simpler form as well as rounding up of the pericytes and loosening of their vascular sheaths indicate remodeling of the vascular wall during chronic diabetes and sustained hypertension, before a characteristic vasculopathy becomes manifest. The combination of diabetes and hypertension enhances these features, as well as basement membrane thickening and breakdown of the blood-retinal barrier.