# Revealing the role of regulatory microglial IRF7-NLRP3 interactions in optic nerve damage of normal-tension glaucoma based on single-cell RNA sequencing

## TL;DR

This study investigates how OPTN (E50K) mutations cause optic nerve damage in normal-tension glaucoma by altering microglial inflammation through IRF7 and NLRP3 interactions.

## Contribution

The study identifies a novel regulatory mechanism involving IRF7-NLRP3 interactions in OPTN (E50K)-related optic nerve damage in normal-tension glaucoma.

## Key findings

- OPTN (E50K) mutations reduce IRF7's suppressive effect on NLRP3, leading to increased microglial inflammation.
- Single-cell RNA sequencing revealed significant inflammatory pathway enrichment in OPTN (E50K) mutant mice.
- Molecular techniques confirmed the interaction between IRF7 and NLRP3 in modulating optic nerve damage.

## Abstract

Normal-tension glaucoma (NTG) is a subtype of primary open-angle glaucoma (POAG). Patients with NTG still experience significant optic nerve damage despite maintaining normal intraocular pressures. The mechanism of optic nerve damage in glaucoma with normal pressure is still unclear. Research has shown that OPTN (E50K) mutations exacerbate the inflammatory response of retinal microglia. However, there is still a lack of evidence on how OPTN (E50K) mutations directly regulate their inflammatory pathways through key molecules. This study explores the role of microglial inflammation caused by the interaction between IRF7 and NLRP3 molecules in NTG optic nerve injury. Single-cell RNA sequencing (scRNA-seq) was employed to analyze retinal microglial cells from both wild-type (WT) and OPTN (E50K) mutant mice. The analysis revealed significant enrichment of inflammatory pathways and a critical role of IRF7 in modulating NLRP3 activation. Techniques such as Western blot (WB), qPCR, immunofluorescence (IF), and molecular docking were utilized to confirm the interactions between IRF7 and NLRP3. The findings demonstrate that the OPTN (E50K) mutation reduces the suppressive effect of IRF7 on NLRP3, leading to a pro-inflammatory microglial phenotype and exacerbating the optic nerve damage of NTG. This study provides a new therapeutic target for the treatment of NTG optic nerve damage.