Journal of Ocular Pharmacology and Therapeutics
Fluocinolone Inhibits VEGF Expression via Glucocorticoid Receptor in Human Retinal Pigment Epithelial (ARPE-19) Cells and TNF-a–Induced Angiogenesis in Chick Chorioallantoic Membrane (CAM)
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To cite this article:
Surya P. Ayalasomayajula, Paul Ashton, Uday B. Kompella. Journal of Ocular Pharmacology and Therapeutics. April 2009, 25(2): 97-104. doi:10.1089/jop.2008.0090.
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Published in Volume: 25 Issue 2: April 8, 2009
Online Ahead of Print: March 14, 2009
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Full Text: • PDF for printing (270 KB) • PDF w/ links (239.2 KB)
Surya P. Ayalasomayajula
University of Nebraska Medical Center, Omaha, Nebraska.
DMPK-ClinPKPD, Novartis Pharmaceuticals Co., East Hanover, New Jersey.
Paul Ashton
pSivida Inc., Watertown, Massachusetts.
Uday B. Kompella
University of Nebraska Medical Center, Omaha, Nebraska.
University of Colorado Denver, Department of Pharmaceutical Sciences, Aurora, Colorado.
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-a–induced angiogenesis in chick chorioallantoic membrane (CAM) assay.
Methods: The dose-dependent effect of fluocinolone (0.0001–1 µM) 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-a–induced angiogenesis was determined using chick chorioallantoic membrane (CAM) assay. The dose-dependent effect of fluocinolone (0.0001–1 µM) 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 µM) treatment prevented inhibition of VEGF secretion and VEGF mRNA expression by fluocinolone (0.1 µM). Fluocinolone (50 ng/egg) inhibited angiogenesis induced by TNF-a. 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-a–induced angiogenesis in chorioallantoic membranes. |
