Fluocinolone inhibits VEGF expression via glucocorticoid receptor in human retinal pigment epithelial (ARPE-19) cells and TNF-alpha-induced angiogenesis in chick chorioallantoic membrane (CAM)

J Ocul Pharmacol Ther. 2009 Apr;25(2):97-103. doi: 10.1089/jop.2008.0090.


Purpose: The purpose of this study was to determine whether fluocinolone inhibits vascular endothelial growth factor (VEGF) expression in a retinal pigment epithelial cell line (ARPE-19) and TNF-alpha-induced angiogenesis in chick chorioallantoic membrane (CAM) assay.

Methods: The dose-dependent effect of fluocinolone (0.0001-1 microM) on VEGF secretion, VEGF mRNA expression, and cytotoxicity was determined in confluent monolayers of ARPE-19 cells using ELISA, RT-PCR, and MTT assay, respectively. The effect of a glucocorticoid receptor antagonist (RU486) on fluocinolone-mediated VEGF expression was determined. The effect of fluocinolone in inhibiting TNF-alpha-induced angiogenesis was determined using chick chorioallantoic membrane (CAM) assay. The dose-dependent effect of fluocinolone (0.0001-1 microM) in inhibiting 1% serum-stimulated ARPE-19 cell proliferation was determined using BrdU labeling assay.

Results: At concentrations devoid of cytotoxicity, fluocinolone inhibited VEGF secretion as well as mRNA expression in ARPE-19 cells. RU486 (1 microM) treatment prevented inhibition of VEGF secretion and VEGF mRNA expression by fluocinolone (0.1 microM). Fluocinolone (50 ng/egg) inhibited angiogenesis induced by TNF-alpha. The ARPE-19 cell proliferation was inhibited by fluocinolone in a dose-dependent manner.

Conclusions: Fluocinolone inhibited VEGF expression in ARPE-19 cells via its glucocorticoid receptor activity. In addition, fluocinolone inhibited proliferation of ARPE-19 cells and TNF-alpha-induced angiogenesis in chorioallantoic membranes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Cell Line
  • Cell Proliferation / drug effects
  • Chick Embryo
  • Chorioallantoic Membrane / blood supply
  • Chorioallantoic Membrane / drug effects*
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Fluocinolone Acetonide / analogs & derivatives*
  • Fluocinolone Acetonide / pharmacology
  • Humans
  • Mifepristone / metabolism
  • Mifepristone / pharmacology
  • Neovascularization, Physiologic / drug effects
  • RNA, Messenger / metabolism
  • Receptors, Glucocorticoid / metabolism*
  • Retinal Pigment Epithelium / cytology
  • Retinal Pigment Epithelium / drug effects*
  • Retinal Pigment Epithelium / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors*
  • Vascular Endothelial Growth Factor A / biosynthesis


  • Angiogenesis Inhibitors
  • RNA, Messenger
  • Receptors, Glucocorticoid
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Fluocinolone Acetonide
  • Mifepristone
  • fluocinolone