Aldose reductase inhibition prevents glucose-induced apoptosis in culturedbovine retinal microvascular pericytes

The pathogenesis of pericyte loss, an initial deficit in the early stage of diabetic retinopathy, remains unclear. Polyol pathway hyperactivity has be en implicated in the pathogenesis of diabetic retinopathy, and recent studi es have suggested that apoptosis may be involved in pericyte loss. The pres ent study was conducted to investigate whether high glucose induces apoptos is in cultured bovine retinal pericytes. The effect of an aldose reductase inhibitor. SNK-860, was also examined. After a 5 day incubation with variou s concentrations of glucose (5.5-40 mM) in the presence or absence of SNK-8 60, the cell viability and the percentages of dead cells were measured. and staining with the TUNEL method and Hoechst 33342, and DNA electrophoresis were performed. High glucose reduced the viability and increased the percen tages of dead cells. TUNEL-positive cells were observed in pericytes under high glucose, but not in those under 5.5 mM glucose. In the staining of nuc lei with Hoechst 33342, the percentage of apoptotic cells in total cells co unted under high glucose was higher than that under 5.5 mM glucose. DNA ele ctrophoresis of pericytes cultured with high glucose demonstrated a 'ladder pattern'. Hyperosmolarity also induced apoptosis in pericytes, but less th an that by high glucose. SNK-860 inhibited the glucose-induced apoptosis in pericytes. These observations suggest that the pericyte loss in diabetic r etinopathy involves an apoptotic process, and that the polyol pathway hyper activity plays an important role in inducing apoptosis in pericytes by high glucose. (C) 2000 Academic Press.