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


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.


CONCLUSIONS
These observations suggest that KIOM-79 acts through an antioxidant mechanism to protect against oxidative stress-induced apoptosis in retinal pericytes.
Kim
Ohn Soon
OS
Diabetic Complications Research Center, Division of Traditional Korean Medicine (TKM) Intergrated Research, Korea Institute of Oriental Medicine, Daejeon, South Korea.
Kim
Junghyun
J
Kim
Chan-Sik
CS
Kim
Nan Hee
NH
Kim
Jin Sook
JS
D000818:Animals; D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000517:prevention & control; D005455:Fluorescent Antibody Technique; D008845:Microinjections; D008856:Microscopy, Fluorescence; D020286:Pericytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D011765:Pyruvaldehyde / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000975:Antioxidants; C517978:KIOM 79; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D011765:Pyruvaldehyde