New insight into the neuroimmune interplay in Pseudomonas aeruginosa keratitis.

PURPOSE: This research aims to reveal the roles of the miR-183/96/182 cluster (miR-183C) in sensory neurons (SN) in the interplay of corneal sensory nerves (CSN) and myeloid cells (MC) during Pseudomonas aeruginosa (PA) keratitis. METHODS: The left corneas of SN-specific (SNS) conditional knockout (CKO) and their wild type (WT) littermates were infected with PA. CSN of these mice express RFP; MC EGFP. Confocal microscopy of corneal flatmount, myeloperoxidase (MPO) assay and plate count were performed. RESULTS: In WT mice, CSN began to degenerate at 3 h-post-infection (hpi), starting from epithelial/subepithelial layers in the central region. By 1 day-post-infection (dpi), epithelium/subepithelial CSN were nearly completely destroyed, while stromal nerves persisted. From 3 dpi, CSN were obliterated in both layers. In CKO vs WT mice, CSN density was decreased at 3 and 6 hpi; however, CNS degeneration followed a slower pace. At 3 dpi, residual large-diameter stromal CSN were better preserved. MC were decreased in the central cornea at 3 and 6 hpi, but increased in the periphery, more prominent in CKO mice. At 12 hpi, densely packed MC formed a ring-shaped band circling a "dark" zone nearly devoid of MC, colocalizing with CSN most degenerated central area. At 1 dpi, the cornea was filled with MC; MC density was lower in CKO. CKO mice had decreased neutrophils at 1 dpi and reduced disease severity at 3 dpi. CONCLUSIONS: Our results provide new insight into the neuroimmune interplay during PA keratitis. miR-183C in CSN modulates PA keratitis through regulation of neuroimmune interaction.