N4BP1 promotes the progression of acute glaucoma by promoting pyroptosis through the JAK2/STAT3 pathway.

Abstract

Acute glaucoma is the common subtype of glaucoma with unclear mechanism, which is characterized by an abrupt increase in intraocular pressure (IOP) leading to irreversible vision loss. To elucidate the mechanisms underlying the progression of acute glaucoma, here we found that N4BP1, a pivotal regulator innate immune signaling and inflammation, is upregulated in acute glaucoma mice. Notably, knockdown of N4BP1 exhibited alleviation of acute glaucoma symptoms, along with a decrease in microglial activation and pyroptosis levels when compared with the ischemia-reperfusion model group. Subsequently, through the analysis of transcriptome sequencing results, we identified pyroptosis and JAK2/STAT3 as the potential downstream targets of N4BP1. We further confirmed that the JAK2/STAT3 pathway is indeed a critical factor in N4BP1-mediated regulation of microglial activity and pyroptosis levels in vitro. In conclusion, N4BP1 could modulate cell pyroptosis and the progression of acute glaucoma through the JAK2/STAT3 signaling pathway, suggesting its potential as a viable molecular target for the clinical treatment of acute glaucoma in the future.