AUTHOR=Sun Xiaowei , Ma Lusheng , Li Xiao , Wang Jiao , Li Yuanbin , Huang Zijing 

TITLE=Ferulic acid alleviates retinal neovascularization by modulating microglia/macrophage polarization through the ROS/NF-κB axis

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.976729

DOI=10.3389/fimmu.2022.976729

ISSN=1664-3224

ABSTRACT=<p>Inflammation plays a pivotal role in ischemia-induced retinal neovascularization. Targeting microglia/macrophage-based neuroinflammation presents a promising therapeutic strategy. Ferulic acid (FA), a natural and active ingredient in plants, exerts favorable anti-oxidative and anti-inflammatory activities. In this study, we investigated the inhibitory effect of FA against hypoxia-induced retinal angiogenesis using cultured retinal vascular endothelial cells and an oxygen-induced retinopathy mouse (OIR) model. The immunoregulatory effect of FA on microglia/macrophage polarization was evaluated by detecting the expression of specific markers for both pro-inflammatory “M1” and anti-inflammatory “M2” phenotypes using co-immunostaining and polymerase chain reaction assays. The underlying molecular mechanism upon FA treatment was also explored. The results showed that FA supplement markedly inhibited retinal pathological angiogenesis both <italic>in vivo</italic> and <italic>in vitro</italic>. In addition, FA switched microglia/macrophage polarization from “M1” towards “M2” phenotype and alleviated the inflammatory response. Mechanically, the anti-angiogenic and anti-inflammatory properties of FA were mainly due to blockade of the ROS/NF-κB pathway. Our data demonstrated an anti-angiogenic effect of FA through regulating M1-to-M2 microglia/macrophage polarization, suggesting a potential therapeutic strategy for retinal neovascular diseases.</p>