KIOM-79 prevents methyglyoxal-induced retinal pericyte apoptosis in vitro and in vivo

Aims of study: The purpose of this study was to investigate the protective effects of KIOM-79, a combination of four plant extracts, on retinal pericytes loss, which is one of the histopathological hallmarks of early diabetic retinopathy. Materials and methods: To investigate the protective effect of KIOM-79 on pericyte apoptosis, we have used methylglyoxal (MGO)-treated primary rat retinal pericytes and retinal vessels from intravitreally MGO-injected eyes. Primary rat retinal pericytes were exposed to 400 mu M MGO for 6 h with or without KIOM-79. 400 mu M final intravitreal concentration of MGO with or without KIOM-79 (10 mu g/ml final intravitreal concentration) were intravitreally injected into the right eyes of rats for 2 days. The left eyes were received 3 mu l of saline only. Retinal vessels were then isolated. We examined apoptosis, ROS productions, 8-OHdG in cultured rat retinal pericytes and retinal vessels. Results: In CCK-8 assay and TUNEL staining, MGO-induced apoptosis of rat retinal pericytes was markedly inhibited by KIOM-79. KIOM-79 significantly reduced intracellular ROS productions and oxidative damage induced by MGO. In addition, the intravitreal injection of KIOM-79 prevented apoptosis of retinal microvascular cells, MGO accumulation and oxidative DNA damage in intravitreally MGO-injected eye. Conclusion: These observations suggest that KIOM-79 acts through an antioxidant mechanism to protect against oxidative stress-induced apoptosis in retinal pericytes. (C) 2010 Elsevier Ireland Ltd. All rights reserved.