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Sorafenib prevents human retinal pigment epithelium cells from light-induced overexpression of VEGF, PDGF and PlGF

Authors :
Anselm Kampik
Claudia S. Alge
Raffael Liegl
M.W. Ulbig
A.S. Neubauer
Marcus Kernt
Christoph Hirneiss
Armin Wolf
Source :
The British journal of ophthalmology. 94(11)
Publication Year :
2010

Abstract

Background Cumulative light exposure is significantly associated with progression of age-related macular degeneration (AMD). Inhibition of vascular endothelial growth factor is the main target of current antiangiogenic treatment strategies in AMD. However, other growth factors, such as platelet-derived growth factor (PDGF) and placenta growth factor (PlGF), have a substantial impact on development of AMD. Previous reports indicate that sorafenib, an oral multikinase inhibitor, might have beneficial effects on exudative AMD. This study investigates the effects of sorafenib on lightinduced overexpression of growth factors in human retinal pigment epithelial (RPE) cells. Methods Primary human RPE cells were exposed to white light and incubated with sorafenib. Viability, expression, and secretion of VEGF-A, PDGF-BB, and PlGF and their mRNA were determined by reverse transcription-polymerase chain reactions, immunohistochemistry and enzyme-linked immunosorbent assays. Results Light exposure decreased cell viability and increased expression and secretion of VEGF-A, PDGF-BB and PlGF. These light-induced effects were significantly reduced when cells were treated with sorafenib at a dose of 1 mg/ml. Conclusion The results show that sorafenib has promising properties as a potential antiangiogenic treatment for AMD.

Details

ISSN :
14682079
Volume :
94
Issue :
11
Database :
OpenAIRE
Journal :
The British journal of ophthalmology
Accession number :
edsair.doi.dedup.....111c62dbbbaea61c3e3d124bbfc71576