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


CONCLUSIONS
The results show that sorafenib has promising properties as a potential antiangiogenic treatment for AMD.
Department of Ophthalmology, Ludwig-Maximilians-University, Munich 80336, Germany. marcus.kernt@med.uni-muenchen.de
M
M
Kernt
A S
AS
Neubauer
R G
RG
Liegl
C
C
Hirneiss
C S
CS
Alge
A
A
Wolf
M W
MW
Ulbig
A
A
Kampik
D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000494:pharmacology*; D002470:Cell Survival; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008027:Light; D008268:Macular Degeneration / Q000188:drug therapy*; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D000077157:Sorafenib; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D020533:Angiogenesis Inhibitors; D001557:Benzenesulfonates; D008565:Membrane Proteins; C098069:PIGF protein, human; D010671:Phenylurea Compounds; D010982:Platelet-Derived Growth Factor; D011725:Pyridines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000077157:Sorafenib