Sinomenine enhances recovery from corneal alkali burns by attenuating macrophage M1 polarization through modulating the METTL3/IRAKM axis.

Abstract

Corneal alkali burns trigger the infiltration of inflammation-associated macrophages, which can potentially lead to vision impairment. Although Sinomenine (SIN) is recognized for its anti-inflammatory properties, its role on the polarization of macrophages and its effects on corneal alkali injury remain inadequately understood. In this study, corneal alkali damage was induced using NaOH. HE staining and immunohistochemistry were conducted to assess macrophage infiltration in corneal tissues. Macrophages were isolated via flow cytometry assay. Quantitative real-time PCR (qRT-PCR) was employed to examine the expression of genes associated with macrophage polarization. The results indicated an increase in macrophage infiltration and M1 polarization in mice subjected to corneal alkali injury. Sinomenine treatment effectively inhibited the polarization of M1 macrophages in the cornea. In mice treated with Sinomenine post-injury, there was a reduction in the expression of the m6A methylation writer protein METTL3 in macrophages, which led to an upregulation of IRAKM expression. The elevated IRAKM expression subsequently inhibited the TLR4 inflammatory pathway and reduced corneal inflammatory cell infiltration, ultimately ameliorating corneal alkali burns. Sinomenine attenuates M1 macrophage polarization through upregulating IRAKM by inhibiting the expression of the m6A methylation writer protein METTL3 in macrophages, leading to enhanced outcomes in corneal alkali injuries.