Sorafenib prevents human retinal pigment epithelium cells from light-induced overexpression of VEGF, PDGF and PlGF
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vor 14 Jahren
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 mu g/ml.
Conclusion The results show that sorafenib has promising properties
as a potential antiangiogenic treatment for AMD.
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 mu g/ml.
Conclusion The results show that sorafenib has promising properties
as a potential antiangiogenic treatment for AMD.
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