Oxyopia Abstract

April 14, 2006
Friday, 4 PM
489 Minor Hall

Inna Maltseva, PhD
Vision Science Graduate Program, School of Optometry, University of California, Berkeley
Host: TBA

Title

A Contact Case: Contact Lens Wear vs. Antimicrobials

Abstract

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 b-defensin-2 (hBD-2). Despite multiple anti-bacterial defense systems, extended use of contact lenses predisposes the cornea to serious infection by Pseudomonas 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 Ba (IkBa) phosphorylation and c-jun N-terminal kinase (SAPK/JNK) activation. These signaling intermediates allow nuclear factor-kB (NF-kB) 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 might suggest key control points for pharmacological intervention during corneal bacterial infection.

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