Inhibition of Vascular Endothelial Growth Factor Synthesis in Human Retinal Pigment Epithelial Cells by Pazopanib

Abstract

Age-related macular degeneration (AMD) is a leading cause of central vision blindness in most developed countries. Several new drugs are now available to attempt to prevent progression or treat AMD, however, they have limited effectiveness and therefore are of limited use. Human retinal pigment epithelial (hRPE) cells have been implicated in pathogenesis of AMD via the synthesis of vascular endothelial growth factor (VEGF), which can result in pathological proliferation of vascular endothelial cells and hRPE cells via tyrosine-kinase signaling pathways. Therefore, tyrosine-kinase inhibitors should be considered as potential pharmaco-therapeutic agents in the prevention and treatment of AMD. Since pazopanib (PZB) is a tyrosine-kinase inhibitor of VEGF-R1/VEGF-R2, we investigated its effect on hRPE cell proliferation and VEGF synthesis. We showed that PZB inhibited hRPE cell proliferation and VEGF synthesis in hRPE cells, and therefore it may be of therapeutic value in AMD.