Methylglyoxal (MGO) is an alpha-dicarbonyl compound produced from triose phosphate intermediates of glycolysis. It reacts rapidly with proteins to produce advanced glycation products. We have studied the effect of MGO modification of fibronectin on retinal capillary cell viability. Our studies show that pericytes grown on MGO-modified fibronectin (FN) undergo enhanced apoptosis through the p38MAPK-mediated oxidative pathway and that alphaB-crystallin, a stress protein present in pericytes, can protect them from MGO-mediated apoptosis. Our studies with vascular endothelial cells show that hyperglycemia-induced apoptosis is inhibited by overexpression of alphaB-crystallin. These observations suggest a novel role of alphaB-crystallin in hyperglycemia-mediated damage to vascular cells in diabetes.