Comparisons between the beneficial effects of different sulphonylurea treatments on ischemia-induced retinal neovascularization.
The aim of this study was to assess the potential beneficial effects of gliclazide and other sulphonylureas on ischemia-induced retinal neovascularization. To produce an animal model of oxygen-induced ischemic retinopathy, 7-day-old (P7) mice were exposed to a 75% oxygen environment for 5 days. On their return to ambient air at P12, these mice were then treated with gliclazide, glibenclamide, glimepiride, or N-acetylcysteine. Gliclazide, but not glibenclamide or glimepiride, markedly suppresses retinal neovascularization. N-Acetylcysteine, however, only moderately suppresses retinal neovascularization. The number of neovascular nuclei in the retinal cross sections decreased by 29% in the gliclazide-treated mice (P<0.05 vs control). The induction of VEGF mRNA expression at P13 is significantly suppressed in the gliclazide group, relative to the control group (-44%, P<0.05). The VEGF protein expression levels at P15 were also suppressed in the gliclazide group (-43%, P<0.01). The 8-isoprostane production levels at P15 were suppressed in both the gliclazide group (-20%, P<0.05) and the N-acetylcysteine-treated group (-31%, P<0.01). Gliclazide inhibits ischemia-induced retinal neovascularization, and this is likely to be mediated in part through the downregulation of VEGF and the suppression of oxidative stress.
Kimura
Tetsushi
T
Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Takagi
Hitoshi
H
Suzuma
Kiyoshi
K
Kita
Mihori
M
Watanabe
Daisuke
D
Yoshimura
Nagahisa
N
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D005260:Female; D005907:Gliclazide / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007511:Ischemia / Q000150:complications; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology; D010100:Oxygen / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D015861:Retinal Neovascularization / Q000188:drug therapy*; D013453:Sulfonylurea Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D001786:Blood Glucose; D012333:RNA, Messenger; D013453:Sulfonylurea Compounds; D042461:Vascular Endothelial Growth Factor A; C057619:glimepiride; D005907:Gliclazide; D010100:Oxygen; D005905:Glyburide; D000111:Acetylcysteine