The influence of advanced glycation end products (AGES) on apoptotic cell death and vascular endothelial growth factor (VEGF) gene expression in cultured bovine retinal pericytes was investigated. When pericytes were incubated with three immunochemically distinct AGES, which were prepared in vitro by incubating bovine serum albumin with glucose, glyceraldehyde, or glycolaldehyde, apoptotic cell death and DNA ladder formation were significantly induced. The cytopathic effects of glyceraldehyde, or glycolaldehyde-derived AGES were significantly enhanced in AGE receptor-transfected pericytes. Furthermore, all of these AGES were found to upregulate the secretory forms of VEGF mRNA levels in retinal pericytes. These results suggest that AGES disturbed retinal microvascular homeostasis by inducing pericyte apoptosis and VEGF overproduction and thus were involved in the pathogenesis of early phase diabetic retinopathy. (C) 2002 Elsevier Science (USA).