Genistein Suppressed Upregulation of Vascular Endothelial Growth Factor Expression by Cobalt Chloride and Hypoxia in Rabbit Retinal Pigment Epithelium Cells

Abstract

The time course changes of vascular endothelial growth factor (VEGF) protein expression induced by cobalt chloride (CoCl₂) and hypoxia and the effects of genistein on CoCl₂- and hypoxia-induced VEGF expression in rabbit retinal pigment epithelium (RPE) cells were studied. Judged by relative fluorescence using a confocal scanning laser microscope coupled to a computer, VEGF protein expression exposed for different periods to CoCl₂ or hypoxia was investigated. CoCl₂ was found to significantly elevate VEGF protein expression. At 4 h after CoCl₂ treatment, the expression of VEGF protein was about three times as much as that at the start of treatment. Genistein (50, 100 and 200 μM) inhibited VEGF protein expression elicited by CoCl₂ in a concentration-dependent manner. Hypoxia (5% CO₂/95% N₂) could markedly increase VEGF protein expression. The elevation of VEGF protein expression was gradual and time-dependently. At 6 h, the highest expression of VEGF protein was observed, it was about three times as much as that at the start of treatment. After preincubation with 50, 100, and 200 μM genistein respectively, the hypoxia-evoked VEGF expression was concentration-dependently suppressed. These results indicated that genistein could be an effective agent in the prevention and treatment of intraretinal and subretinal neovascularization.