THE EFFECT OF AMINOGUANIDINE AND TOLRESTAT ON GLUCOSE TOXICITY IN BOVINE RETINAL CAPILLARY PERICYTES

Cultured bovine retinal capillary pericytes (BRP) were used to investi gate the effect; of an aldose reductase inhibitor, tolrestat, and an i nhibitor of advanced glycation end products (AGE) formation, aminoguan idine, on glucose toxicity. Glucose at high concentration reduced the replicative activity of pericytes in a dose-dependent manner. Tolresta t completely inhibited the production of sorbitol in cells exposed to a high concentration of glucose but;failed to protect the cells from g lucose toxicity. These results suggest that sorbitol accumulation in c ells is probably not the major mechanism for glucose toxicity. In cont rast, the addition of aminoguanidine at 10 mM concentration to the cul ture media protected pericytes from glucose toxicity. The degree of pr otection was dose-dependent and evident at aminoguanidine concentratio n as low as 1 mM. The drug was only slightly toxic to BRP but induced morphological changes in pericytes with the loss of cellular processes and decreased cell spreading. This may suggest some action of aminogu anidine on the pericyte cytoskeleton. High concentration of glucose si gnificantly increased the level of early glycation but not fluorescent AGE formation on BRP proteins. This was inhibited by the addition of aminoguanidine suggesting that glycation of cellular/membrane proteins and other mechanisms may play an important role in the toxic action o f high glucose levels in cultured pericytes.