Absence of CX3CR1 reduces dry eye disease-related inflammation in cornea of mice

Abstract

Purpose : In dry eye disease (DED), inflammation plays a crucial role in sustaining ocular surface inflammation and causing chronic ocular pain symptoms. Chemokines and their receptors, particularly CX3CL1 and CX3CR1, are key inflammatory mediators. Despite ample evidence on CX3CL1, the significance of CX3CR1 in inflammatory ocular surface diseases remains poorly understood. We aimed to investigated the role of CX3CR1/CX3CL1 in the inflammatory responses of the cornea in a in vivo benzalkonium chloride (BAC)-induced model of DED.

Methods : Adult male C57BL/6J mice and Cx3cr1^−/− transgenic mice (n=10 per group) developed DED by chronic topical instillation of 0.2% BAC (10µl, twice a day, 7 days). Control animals received topical PBS. A panel of methodological approaches were used to monitor the impact of Cx3cr1 deficiency on ocular pain-related behaviors (spontaneous ocular discomfort, von Frey mechanical sensitivity test) and on morphological and cellular changes (in vivo confocal imaging, slit lamp imaging, corneal thickness, immune cells and CX3CR1 immunohistochemistry, flow cytometry) occurring in the ocular surface.

Results : Topical administration of 0.2% BAC increased CX3CR1 expression in WT cornea. Subsequently, Cx3cr1^−/− mice exhibited comparable levels of epithelial corneal damage, ocular discomfort and corneal hypersensitivity after BAC exposure compared to WT mice. We next reported that Cx3cr1 deficiency not only prevented the BAC-induced increase in corneal thickness but also resulted in a reduction of the number of corneal inflammatory cells compared to WT mice.

Conclusions : Our results suggest the importance of CX3CR1 in DED-related inflammatory responses. This study opens new research opportunities in CX3CR1-related inflammation in ocular surface diseases and suggests that CX3CR1 may represent a novel therapeutic target for alleviating DED-related inflammation.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.