Anionic sites in diabetic basement membranes and their possible role in diffusion barrier abnormalities in the BB-rat

Basement membrane anionic sites, thought to be responsible for charge selective permeability barriers, were investigated in retinal, endoneurial, and muscle capillary basement membranes and in Bruch's membrane of diabetic, and age- and sex-matched non-diabetic BB-rats using an ultrastructural quantitative histochemical technique. Six months of diabetes was associated with significant basement membrane thickening which was linearly related to a decrease in anionic site density suggesting a relative loss of proteoglycans. Calculation of anionic sites per unit length of basement membrane, reflecting their absolute number, revealed a significant loss in basement membrane, constituting part of normal blood-tissue barrier systems such as retinal and endoneurial capillary basement membranes, and the basement membrane of the retinal pigment epithelium. The absolute number of anionic sites in normally permeable microvessels, such as those of muscle and choriocapillaries, was unaltered by diabetes. We conclude that this specific loss of anionic sites in basement membranes of tissues affected by chronic diabetic complications may in part be responsible for permeability abnormalities seen in these tissues.