Abstract: This dissertation evaluates an effect of contact lens wear on corneal epithelial cells ability to respond to Pseudomonas aeruginosa in vitro . Microbial keratitis is one of the most destructive diseases of the cornea. It is characterized by extensive ulceration and dissolution of the corneal stroma leading to blindness. To prevent this, the human eye produces a spectrum of antimicrobial peptides including human β-defensin-2 (hBD-2). Its expression is dramatically induced by various stimuli including Gram-negative bacteria, inflammation and corneal injury. Despite multiple anti-bacterial defense systems, extended use of contact lenses predisposes the cornea to serious infection by Pseudomonas aeruginosa. We hypothesized that the severe P. aeruginosa infections seen in contact lens wearers occur due to a deficiency in the ability of corneal cells to up-regulate defensin transcription in response to P. aeruginosa. We have reproduced this phenomenon in vitro, and observed that it is correlated with a profound defect in the ability of corneal cells to produce hBD-2 in response to P. aeruginosa culture supernatant. To understand this defect we investigated the mechanisms controlling the production of hBD-2 by corneal cells in response to bacteria in the absence of contact lenses. This allowed for comparisons between contact lens-exposed and non-exposed cells. It was found that P. aeruginosa-induced hBD-2 up-regulation requires Toll-like receptor mediated signaling events that involve inhibitory kappa Bα (IκBα) phosphorylation and c-jun N-terminal kinase (SAPK/JNK) activation. These signaling intermediates allow nuclear factor-κB (NF-κB) and activation protein 1 (AP-1) respectively to stimulate gene transcription. Finally, it was determined that contact lens wear interferes with JNK and AP-1 activation evoked by Pseudomonas aeruginosa. The results presented in this dissertation might suggest key control points for pharmacological intervention during corneal bacterial infection.