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Sorafenib protects human optic nerve head astrocytes from light-induced overexpression of vascular endothelial growth
M Kernt1, R G Liegl, J Rueping
1Department of Ophthalmology, Ludwig-Maximilians University, 80336 Munich, Germany. marcus.kernt@med.uni-muenchen.de
Objectives:
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.
Conclusion:
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.
Insights
Sorafenib treatment significantly reduced light-induced growth factor overexpression in human retinal glial cells, showing potential for treating retinal neovascular diseases.
Area of Science:
- Ophthalmology
- Molecular Biology
- Cell Biology
Background:
- Retinal neovascular diseases like diabetic retinopathy and age-related macular degeneration involve growth factors such as VEGF, PDGF, and PlGF.
- Glial cells are a primary source of these growth factors in the retina.
- Excessive light exposure can increase retinal growth factor production.
Purpose of the Study:
- To investigate the impact of sorafenib on growth factor expression in human retinal glial cells exposed to light.
- To determine if sorafenib can mitigate light-induced overexpression of VEGF, PDGF, and PlGF.
Main Methods:
- Primary human optic nerve head astrocytes (ONHAs) were subjected to white light exposure.
- Cells were treated with sorafenib, a multikinase inhibitor.
- VEGF-A, PDGF-BB, and PlGF expression and secretion were analyzed using RT-PCR, immunohistochemistry, and ELISA.
Main Results:
- Light exposure reduced ONHA viability and increased VEGF-A, PDGF-BB, and PlGF expression and secretion.
- Sorafenib treatment (1 microg/ml) significantly counteracted these light-induced effects.
- The drug effectively reduced the overexpression of key growth factors.
Conclusions:
- Sorafenib demonstrates a significant inhibitory effect on light-induced VEGF-A, PDGF-BB, and PlGF overexpression in human retinal glial cells.
- These findings suggest sorafenib holds promise as a potential therapeutic agent for managing retinal neovascularization.
