Invest Ophthalmol Vis Sci. 2026 Jul 1;67(8):27. doi: 10.1167/iovs.67.8.27.
ABSTRACT
PURPOSE: Rheumatoid arthritis (RA) is an autoimmune disease often associated with corneal ulceration and impaired corneal epithelial wound healing (CEWH), although the underlying cause remains unclear. This study aims to elucidate the pathogenic mechanism of RA-associated delayed CEWH.
METHODS: We integrated analyses of human clinical samples, a murine collagen-induced arthritis (CIA) model, a human corneal epithelial cell (HCEC) culture platform, as well as Olink proteomic and transcriptomic analysis. We characterized RA-related ocular phenotypes, evaluated the effects of IL-1α/IFN-γ on HCECs, and validated interventions using the NLRP3 inflammasome inhibitor MCC950.
RESULTS: RA patients exhibited delayed CEWH, reduced tear secretion, and heightened ocular surface inflammation characterized by elevated Oncostatin M (OSM), IL-1α and IFN-γ. OSM alone promoted the proliferation and migration of HCECs and enhanced mitochondrial respiratory capacity. However, these beneficial effects were markedly impaired when OSM-treated HCECs were co-exposed to IL-1α and IFN-γ, an effect accompanied by severe mitochondrial damage, compromised oxidative phosphorylation, and increased NLRP3 inflammasome activity. Notably, pharmacological blockade of NLRP3 inflammasome with MCC950 significantly restored HCEC functions compromised by IL-1α/IFN-γ exposure, with improved mitochondrial ultrastructure and function. Furthermore, topical MCC950 administration accelerated CEWH in the CIA model.
CONCLUSIONS: Ocular IL-1α/IFN-γ impairs corneal epithelial function by disrupting mitochondrial integrity and amplifying NLRP3-mediated inflammatory cascades, thereby contributing to delayed CEWH in RA patients.
PMID:42417589 | DOI:10.1167/iovs.67.8.27