Tocilizumab attenuates choroidal neovascularization by regulating macrophage polarization through the IL-6R/STAT3/VEGF pathway.

Globally, age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment. Up to 80% of severe vision loss is caused by AMD, which is characterized by the development of choroidal neovascularization (CNV). Uncertainty exists regarding the precise pathophysiological mechanisms of CNV. It has been suggested that the interleukin (IL) IL-6/IL-6R signaling pathway is crucial in the progression of CNV. Tocilizumab (TCZ), a monoclonal antibody, binds to soluble and membrane-bound IL-6R and competitively inhibits IL-6 downstream signaling. Previous research has demonstrated that TCZ promotes several roles related to inflammation and neovascularization. However, the effects of TCZ on CNV and the underlying mechanism are still unknown. This study found that TCZ administration decreased the area and leakage of CNV lesions in the mice model of laser-induced CNV. Additionally, results demonstrated that TCZ promotes the expression of iNOS, CCL-3, CCL-5, TNF-α and inhibits the expression of Arg-1, IL-10, YM-1 and CD206. Furthermore, TCZ treatment inhibited the signal transducer and activator of transcription (STAT) STAT3/vascular endothelial growth factor (VEGF) pathway, which was activated after CNV formation. Colivelin, a STAT3 agonist, reversed the inhibitory effects of TCZ on CNV formation and macrophage polarization. In a mouse model of laser-induced CNV, our findings demonstrated that TCZ attenuated CNV formation and inhibited the leakage of CNV lesions by regulating macrophage polarization via inhibiting the STAT3/VEGF axis. TCZ is the potential therapeutic strategy for CNV.