Vascular endothelial growth factor reduced and connective tissue growth factor induced by triamcinolone in ARPE19 cells under oxidative stress.

PURPOSE: To investigate whether triamcinolone acetonide (TA) affects the expression of vascular endothelial growth factor (VEGF) and connective tissue growth factor (CTGF) in retinal pigment epithelial (RPE) cells exposed to oxidative stress.

METHODS: TA (10 nM, 1 microM, or 100 microM) was added to ARPE19 cells exposed to oxidative stress induced by hypoxia-reoxygenation and paraquat. Cellular expression of VEGF, CTGF, and an inducer of both growth factors, transforming growth factor (TGF)-beta was investigated with real-time reverse transcription-polymerase chain reaction and Western blot analysis. Tube-forming assays were conducted with human umbilical vein endothelial cells (HUVECs) in conditioned medium from RPE cells exposed to oxidative stress, with or without TA treatment.

RESULTS: Oxidative stress induced mRNA expression of VEGF, CTGF, and TGF-beta by RPE cells. TA reduced upregulation of VEGF and TGF-beta in a concentration-dependent manner. In contrast, upregulation of CTGF by oxidative stress was accelerated by TA concentrations of 10 nM and 1 muM. Tube formation by HUVECs was strongly inhibited by exposure to conditioned medium from oxidative stress-stimulated ARPE19 cells treated with 1 muM TA compared with cells not treated with TA.

CONCLUSIONS: TA reduced VEGF expression and induced CTGF expression in ARPE19 cells exposed to oxidative stress, and conditioned medium from these cells inhibited tube formation by HUVECs. Because VEGF is a major cytokine involved in angiogenesis, and CTGF is a main cytokine related to fibrosis, these results suggest that changes in their expression may be important mechanisms underlying the decreased choroidal neovascularization and fibrosis after administration of TA.