The role of neutrophils in the regeneration of corneal nerve injury

Abstract

Abstract Background To investigate the role of neutrophils in the regeneration of corneal nerve injury. Methods A mouse model of a corneal nerve injury was established, samples from with and without neutrophil closure in corneal scraping were collected for corneal nerve staining, RNA sequencing, and bioinformatics. Differential expression analysis between these two groups was performed for enrichment analysis. The differential genes were then intersected with neutrophil-associated genes, and the obtained intersected genes were subjected to protein-protein interaction (PPI) network construction. The immune infiltration between the two groups was observed as well as the variation of immune cells between the high and low gene expression groups. Results Removal of neutrophils delays the regeneration of corneal epithelium and nerves. A total of 546 differential genes and 980 neutrophil-associated genes, with 27 genes common to both were obtained. Molecular complex assay (MCODE) analysis yielded five key genes, ITGB2, MMP9, EGF, SERPINE1, and PLAUR. ITGB2, SERPINE1, and PLAUR demonstrated increased high expression in the neutrophil-confined group and decreased expression of MMP9 and EGF, and the difference was more significant for MMP9 and EGF. The immune infiltration was also observed between the two groups. The infiltration of M0 macrophages activated mast cells, and neutrophils were significantly different between the two groups. The levels of neutrophils were also shown to be lower in the MMP9 and EGF low expression groups and higher in the high expression group. Conclusion Neutrophil confinement may significantly affect the expression levels of MMP9 and EGF. Strategies to inhibit MMP9 may have potential therapeutic benefits.