[Cytoprotective and antiangiogenic effects of the multikinase inhibitor sorafenib on human retinal pigmentepithelium].
BACKGROUND
Cumulative light exposure is significantly associated with progression of age-related macular degeneration (AMD). Inhibition of vascular endothelial growth factor A (VEGF) is the main target of current antiangiogenic treatment strategies for AMD. Previous reports indicated that sorafenib, an oral multikinase inhibitor, might have beneficial effects on exudative AMD. This study investigates the effects of sorafenib on light-induced overexpression of VEGF and its receptors VEGFR1 and 2 in human retinal pigment epithelial (RPE) cells.


METHODS
The effects of sorafenib on VEGFR1 and 2 expression of primary human RPE cells was investigated by reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and western blotting. In addition, RPE cells were exposed to white light and incubated with sorafenib. Viability, expression of VEGF and its mRNA were determined by RT-PCR, immunohistochemistry, western blotting, and enzyme-linked immunosorbent assays.


RESULTS
Sorafenib reduced VEGFR1 and 2 expression of RPE cells. Light exposure decreased cell viability and increased expression and secretion of VEGF. These light-induced effects were significantly reduced when cells were treated with sorafenib at a dose of 1 µg/ml.


CONCLUSIONS
The results show that sorafenib has promising properties as a potential antiangiogenic treatment for AMD.
Augenklinik, Ludwig-Maximilians-Universität, München, Deutschland. Marcus.Kernt@med.uni-muenchen.de
M
M
Kernt
S
S
Thiele
C
C
Hirneiss
A S
AS
Neubauer
C A
CA
Lackerbauer
A
A
Wolf
K H
KH
Eibl
C
C
Haritoglou
M W
MW
Ulbig
A
A
Kampik
D000328:Adult; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D001557:Benzenesulfonates / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism*; D000077157:Sorafenib; D016896:Treatment Outcome; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D055815:Young Adult
D020533:Angiogenesis Inhibitors; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2
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