Mitochondrial dysfunction and NLRP3 inflammasome activation jointly delay corneal wound healing in rheumatoid arthritis

This study aimed to investigate the intrinsic mechanism underlying impaired corneal epithelial wound healing in patients with rheumatoid arthritis (RA). First, the corneal epithelial wound healing status was compared between RA patients and healthy individuals. Subsequently, validation was performed using a collagen-induced arthritis (CIA) mouse model. Combined with differential results from proteomic screening, studies were conducted through treatment with differential inflammatory factors, detection of cell proliferation, colony formation and migration functions, mitochondrial function analysis, and NOD-like receptor pathway blocking experiments. The results showed that corneal epithelial wound healing was significantly delayed in both RA patients and CIA mice, with their ocular surfaces in a state of chronic inflammation. Chronic inflammation impaired the function of corneal epithelial stem/progenitor cells. Based on transcriptomic screening results, this impairment was associated with abnormalities in mitochondrial morphology and function. Further studies revealed that activation of the NLRP3 inflammasome played a key role in this process. Blocking the NLRP3 inflammasome with a specific inhibitor (MCC950) effectively improved the function of corneal epithelial stem/progenitor cells and promoted corneal epithelial wound healing in CIA mice. This study reveals the key mechanism by which chronic inflammation affects corneal epithelial wound healing through activating the NLRP3 inflammasome, providing a new direction for the subsequent development of therapeutic methods targeting RA-related corneal injury.