MODIFICATION OF ENZYMATIC ANTIOXIDANTS IN RETINAL MICROVASCULAR CELLSBY GLUCOSE OR ADVANCED GLYCATION END-PRODUCTS

Oxidative stress is one possible pathogenic mechanism to explain diabe tic microangiopathy. In the present study, we determined the antioxida nt enzyme activities in bovine retinal microvessels and cultured retin al microvascular cells: endothelial cells (BREC) and pericytes (BRP). We further investigated the effects of high glucose and advanced glyca tion end products (AGE) on these enzyme activities in BREC and BRP. An tioxidant enzyme activities in native retinal microvessels and BREC we re quite similar but differed markedly from the BRP ones. High glucose decreased Se-GPx activity (about 20%) in BREC compared to mannitol. H igh concentrations of mannitol or NaCl increased Se-GPx activity (up t o 40%) compared to control medium, suggesting that hyperosmolarity cou ld regulate Se-GPx in BREC. No changes in antioxidant enzyme activitie s were observed when BRP were cultured with glucose or mannitol at hig h concentrations. AGE-BSA had no effect on enzyme activities in BREC, whereas 20 mu M AGE-BSA increased catalase (40%) and superoxide dismut ase (60%) activities in BRP. Differences in antioxidant enzyme activit ies observed between BREC and BRP, cultured with high concentrations o f glucose or AGE, might help to explain their different behavior durin g the pathogenesis of diabetic retinopathy, i.e., early pericyte drop- out and late endothelial cell proliferation. (C) 1998 Elsevier Science Inc.