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Sarah Thiele, Aljoscha S. Neubauer, Kirsten Eibl, Armin Wolf, Michael W. Ulbig, Anselm Kampik, Marcus Kernt; Inhibitory Activity Of Ranibizumab, Sorafenib, And Pazopanib On Light-induced Overexpression Of PDGF And VEGF And The Receptors VEGFR-1, VEGFR-2, Neuropilin-1, And Neuropilin-2. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2350.
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Cumulative light exposure is significantly associated with progression of age-related macular degeneration (AMD). Growth factors and growth factor receptor signaling are known to have a substantial impact on the development of AMD. This study explored the effects of ranibizumab, sorafenib, and pazopanib on vascular endothelial growth factor A (VEGF) receptor 1 and 2 (VEGFR-1 and -2) and neuropilin 1 and 2 (NP-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 (PDGF) were investigated.
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 VEGFR-1 and -2, NP-1 and -2, and their mRNA, and secretion of VEGF and PDGF were investigated by reverse transcription polymerase chain reactions, immunohistochemistry, and enzyme-linked immunosorbent assays.
Treatment with sorafenib or pazopanib reduced the expression of VEGFR-1 and -2 and NP-1, and sorafenib also reduced NP-2. Light exposure decreased cell viability and increased expression and secretion of VEGF and PDGF. Sorafenib and pazopanib significantly reduced light-induced overexpression and secretion of VEGF and PDGF. Ranibizumab reduced secreted VEGF in cell culture supernatants only.
Our in vitro results suggest that multikinase inhibitors have promising properties as a potentialanti-angiogenic treatment for AMD.
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