Sorafenib protects human optic nerve head astrocytes from light-induced overexpression of vascular endothelial growth factor, platelet-derived growth factor, and placenta growth factor.
OBJECTIVE
Growth factors, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and placenta growth factor (PlGF) are key players in the development of diabetic retinopathy, age-related macular degeneration, and other retinal neovascular diseases. Glial cells provide a significant source of retinal growth factor production under physiologic and pathologic conditions. Cumulative light exposure has been linked to increased retinal growth factor expression. Previous reports indicate that sorafenib, an oral multikinase inhibitor, might have a beneficial effect on retinal neovascularization. This study was designed to investigate the effects of sorafenib on light-induced overexpression of growth factors in human retinal glial cells.


METHODS
Primary human optic nerve head astrocytes (ONHAs) 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 reaction, immunohistochemistry, and enzyme-linked immunosorbent assay.


RESULTS
Light exposure decreased cell viability and increased VEGF-A, PDGF-BB, and PlGF expression and secretion. These light-induced effects were significantly reduced when cells were treated with sorafenib at a concentration of 1 microg/ml.


CONCLUSIONS
Sorafenib significantly reduced light-induced overexpression of VEGF-A, PDGF-BB, and PlGF in primary human ONHAs. Sorafenib has promising properties as a potential supportive treatment for retinal neovascularization.
Kernt
M
M
Department of Ophthalmology, Ludwig-Maximilians University, 80336 Munich, Germany. marcus.kernt@med.uni-muenchen.de
Liegl
R G
RG
Rueping
J
J
Neubauer
A S
AS
Haritoglou
C
C
Lackerbauer
C A
CA
Eibl
K H
KH
Ulbig
M W
MW
Kampik
A
A
D000328:Adult; D000368:Aged; D001253:Astrocytes / Q000187:drug effects / Q000528:radiation effects; D001557:Benzenesulfonates / Q000494:pharmacology* / Q000627:therapeutic use; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008027:Light / Q000009:adverse effects; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D009898:Optic Disk / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D010671:Phenylurea Compounds; D000072483:Placenta Growth Factor; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D015861:Retinal Neovascularization / Q000188:drug therapy; D000077157:Sorafenib; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D001557:Benzenesulfonates; C000608036:PGF protein, human; D010671:Phenylurea Compounds; D010982:Platelet-Derived Growth Factor; D011257:Pregnancy Proteins; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D009536:Niacinamide; D000077157:Sorafenib