Choroidal neovascularization (CNV) is a type of wet age-related macular degeneration (AMD) which is a major cause of blindness in elder patients. Tumor necrosis factor receptor-associated factor 6 (TRAF6) promotes tumor angiogenesis via upregulating the expression of hypoxia-inducible factor 1 alpha (HIF-1 alpha) and vascular endothelial growth factor (VEGF). Additionally, TRAF6 facilitates the inflammatory response in macrophages and microglia. Here, using mouse laser-induced CNV model and TRAF6 siRNA, the study shows that TRAF6 is a critical player in CNV. The expression of TRAF6, HIF-1 alpha, and VEGF increased in the model. TFAF6 siRNA intravitreal (IVT) injection inhibited CNV formation, as well as expression of HIF-1 alpha and VEGF, activation of macrophages and microglia. Together, our data suggest that TFAF6 inhibition reduces CNV formation via down-regulating expression of HIF-1 alpha and VEGF and activation of macrophages and microglia, demonstrating the unique advantages of TRAF6 inhibition in the alleviation of AMD. (C) 2018 Elsevier Inc. All rights reserved.