Extended Contact Lens Wear Promotes Corneal Norepinephrine Secretion and Pseudomonas aeruginosa Infection in Mice

PURPOSE: Extended contact lens (CL) wear predisposes the wearer to Pseudomonas aeruginosa infection of the cornea, but the mechanism involved remains incompletely understood. The purpose of this study was to investigate the role of the stress hormone norepinephrine (NE) in the pathogenesis of CL-induced P. aeruginosa keratitis. METHODS: A total 195 adult C57BL/6 mice were used in this study. Corneal NE content was measured after 48 hours of sterile CL wear in mice. The effect of NE on P. aeruginosa adhesion and biofilm formation on the CL surface was examined in vitro. Moreover, mouse eyes were covered with P. aeruginosa-contaminated CLs, and either 500-µM NE was topically applied or the eyes were subconjunctivally injected with 100 µg of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) to deplete local NE. Clinical scores, neutrophil infiltration, proinflammatory cytokine levels, and bacterial load on the corneas and CLs were evaluated. RESULTS: Corneal NE content was elevated with extended CL wear in mice. In vitro, NE promoted the adhesion and biofilm formation of P. aeruginosa on the CL surface. In mice, topical application of NE aggravated P. aeruginosa infection, accompanied with increased clinical scores, neutrophil infiltration, proinflammatory cytokine expression, and bacterial burden on the corneas and CLs. However, pre-depletion of local NE with DSP-4 significantly alleviated the severity of P. aeruginosa keratitis. CONCLUSIONS: Extended CL wear elevates corneal NE content, which promotes the pathogenesis of CL-induced P. aeruginosa keratitis in mice. Targeting NE may provide a potential strategy for the treatment of CL-related corneal infection caused by P. aeruginosa.