ANTI-GLYCATED ALBUMIN THERAPY AMELIORATES EARLY RETINAL MICROVASCULARPATHOLOGY IN DB DB MICE/

Hyperglycemia plays a primary causal pole in the early vascular damage leading to diabetic retinopathy, but the intermediate biochemical mec hanisms involved are not known. Because albumin modified by Amadori gl ucose adducts has been implicated in the pathogenesis of diabetic neph ropathy, we investigated whether or not glycated albumin plays a simil ar role in diabetic retinopathy. We observed basement membrane thicken ing and an accumulation of basement membrane material in the capillari es of the outer plexiform layer of retinae from diabetic db/db mice co mpared with their nondiabetic db/m littermates, Both of these abnormal ities were ameliorated by chronic (8 week) treatment with monoclonal a ntibodies that specifically recognize Amadori-modified glycated albumi n (and not other glucose-modified or advanced glycation endproducts-mo dified proteins), despite the fact that the administration of these an tibodies did not alter the glycemic status of the diabetic animals. Th us, albumin containing Amadori glucose adducts contributes to the path ogenesis of diabetic retinal vascular disease, and agents that neutral ize or prevent the formation of excess glycated albumin in diabetes ma y offer prophylaxis against the early changes of diabetic retinopathy. (C) 1998 Elsevier Science Inc.