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[Cytoprotective and Antiangiogenic Effects of the Multikinase Inhibitor Sorafenib on Human Retinal Pigmentepithelium]

Overview
Journal Ophthalmologe
Specialty Ophthalmology
Date 2011 Jan 22
PMID 21253747
Citations 3
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Abstract

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.

Conclusion: The results show that sorafenib has promising properties as a potential antiangiogenic treatment for AMD.

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PMID: 37896180 PMC: 10610393. DOI: 10.3390/pharmaceutics15102419.


Medication Trends for Age-Related Macular Degeneration.

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Inhibition of retinopathy of prematurity in rat by intravitreal injection of sorafenib.

Tian L, Ren B, Gao X, Luo Y, Cai Y, Zhou K Int J Ophthalmol. 2014; 7(2):198-204.

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References
1.
Freyberger H, Brocker M, Yakut H, Hammer J, Effert R, Schifferdecker E . Increased levels of platelet-derived growth factor in vitreous fluid of patients with proliferative diabetic retinopathy. Exp Clin Endocrinol Diabetes. 2000; 108(2):106-9. DOI: 10.1055/s-2000-5803. View

2.
Miyamoto N, De Kozak Y, Jeanny J, Glotin A, Mascarelli F, Massin P . Placental growth factor-1 and epithelial haemato-retinal barrier breakdown: potential implication in the pathogenesis of diabetic retinopathy. Diabetologia. 2006; 50(2):461-70. DOI: 10.1007/s00125-006-0539-2. View

3.
Liu L, Cao Y, Chen C, Zhang X, McNabola A, Wilkie D . Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res. 2006; 66(24):11851-8. DOI: 10.1158/0008-5472.CAN-06-1377. View

4.
Mosmann T . Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1-2):55-63. DOI: 10.1016/0022-1759(83)90303-4. View

5.
Kernt M, Liegl R, Rueping J, Neubauer A, Haritoglou C, Lackerbauer C . Sorafenib protects human optic nerve head astrocytes from light-induced overexpression of vascular endothelial growth factor, platelet-derived growth factor, and placenta growth factor. Growth Factors. 2010; 28(3):211-20. DOI: 10.3109/08977191003604505. View