Prodrug of epigallocatechin-3-gallate alleviates choroidal neovascularization via down-regulating HIF-1 alpha/VEGF/VEGFR2 pathway and M1 type macrophage/microglia polarization

摘要

Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly and is attributed to choroidal neovascularization (CNV), which is a feature of wet AMD. The hypoxia-inducible factor-1 alpha (HIF-1 alpha)/vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) pathway contributes to the pathogenesis of CNV. M1-type macrophages/microglia secrete interleukin-6 (IL-6) and tumor necrosis factor a (TNF-alpha), facilitating the development of CNV. Epigallocatechin-3-gallate (EGCG) is a kind of polyphenol in green tea that exerts anti-inflammatory and antiangiogenic effects. In this study, a prodrug of EGCG (pro-EGCG) alleviated mouse laser-induced CNV leakage and reduced CNV area by down-regulating HIF-1 alpha/VEGF/VEGFR2 pathway; M1-type macrophage/microglia polarization; as well as endothelial cell viability, proliferation, migration and tube formation, indicating a novel potential therapy for AMD.