Neuroprotectin D1 regulating the inflammation and nerve restoration in Aspergillus fumigatus keratitis

AIM: ) keratitis in C57BL/6 mice. METHODS: . Each mouse was injected intraperitoneally with 2 µg NPD1 at 1, 3, and 5d post infection (p.i.) and injected subconjunctivally with 5 µL NPD1 once a day. The severity of keratitis was observed by slit lamp and classified by clinical score at 1, 3, and 5d p.i. Hematoxylin and eosin (HE) staining was used to evaluate the histological changes and inflammatory cell infiltration of corneas at 3 and 5d p.i. Polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and Western blot were performed to detect the expression of IL-1β, MIP-2, CGRP, p-p38/p38 MAPK, Nrf-2, and HO-1. Immunofluorescence staining was utilized to assess the neutrophil infiltration and neural innervation. Flow cytometry assay was performed to test the number of total, M1 and M2 macrophages. RESULTS: macrophages, reduced the phosphorylation level of p38 MAPK, and enhanced the expression of Nrf-2/HO-1 at 3d p.i. The number of corneal nerves and the mechanical sensitivity threshold of the NPD1 treatment group were significantly higher than the PBS group at 3 and 5d p.i. Meanwhile, the expression of IL-1β and MIP-2 in the NPD1 treatment group was significantly lower at 3 and 5d p.i. CONCLUSION: keratitis in mice by inhibiting the recruitment of neutrophils and macrophages, promoting M2 macrophage polarization and corneal nerve regeneration.