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

J Ethnopharmacol. 2010 Jun 16;129(3):285-92. doi: 10.1016/j.jep.2010.03.027. Epub 2010 Apr 1.

Abstract

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 microM MGO for 6h with or without KIOM-79. 400 microM final intravitreal concentration of MGO with or without KIOM-79 (10 microg/ml final intravitreal concentration) were intravitreally injected into the right eyes of rats for 2 days. The left eyes were received 3mul 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects*
  • Cell Survival / drug effects
  • Cells, Cultured
  • Diabetic Retinopathy / prevention & control
  • Fluorescent Antibody Technique
  • Microinjections
  • Microscopy, Fluorescence
  • Pericytes / drug effects*
  • Pericytes / metabolism
  • Pericytes / pathology
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Pyruvaldehyde / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Retina / drug effects*
  • Retina / metabolism
  • Retina / pathology
  • Retinal Vessels / drug effects
  • Retinal Vessels / metabolism
  • Retinal Vessels / pathology

Substances

  • Antioxidants
  • KIOM 79
  • Plant Extracts
  • Reactive Oxygen Species
  • Pyruvaldehyde