Inhibitory activity of ranibizumab, sorafenib, and pazopanib on light-induced overexpression of platelet-derived growth factor and vascular endothelial growth factor a and the vascular endothelial growth factor a receptors 1 and 2 and neuropilin 1 and 2

摘要

Background: Cumulative light exposure is significantly associated with progression of age-related macular degeneration. Growth factors and growth factor receptor signaling are known to have a substantial impact on the development of age-related macular degeneration. This study explored the effects of ranibizumab, sorafenib, and pazopanib on vascular endothelial growth factor A (VEGF) receptors 1 and 2 and neuropilin 1 and 2 expression in human retinal pigment epithelial cells. In addition, their effects on light-induced overexpression of VEGF and platelet-derived growth factor were investigated. Methods: Primary human retinal pigment epithelial cells were exposed to white light and then treated with ranibizumab (0.125 mg/mL), sorafenib (1 μg/mL), or pazopanib (1 μg/mL). Viability of cells, expression of VEGF receptors 1 and 2 and neuropilin 1 and 2 and their mRNA, and secretion of VEGF and platelet-derived growth factor were investigated by reverse transcription- polymerase chain reactions, immunohistochemistry, and enzyme-linked immunosorbent assays. Results: Treatment with sorafenib or pazopanib reduced the expression of VEGF receptors 1 and 2 and neuropilin 1, and sorafenib also reduced neuropilin 2. Light exposure decreased cell viability and increased expression and secretion of VEGF and platelet-derived growth factor. Sorafenib and pazopanib significantly reduced light-induced overexpression and secretion of VEGF and platelet-derived growth factor. Ranibizumab reduced secreted VEGF in cell culture supernatants only. Conclusion: Our in vitro results suggest that multikinase inhibitors have promising properties as a potential antiangiogenic treatment for age-related macular degeneration.