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S. R. Heimer, J. J. Mun, M. E. Stern, D. J. Evans, S. M. Fleiszig; Ocular Resistance to Pseudomonas aeruginosa Infection in a Murine Model of Dry Eye Disease. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3897.
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Dry eye disease is thought to associate with increased susceptibility to infection, yet little is known of the mechanisms involved. Our studies with P. aeruginosa suggest tear fluid plays a complex role in protecting against infection, affecting both bacterial virulence and corneal defense. We hypothesized that the induction of dry eye disease in a murine experimental model would reduce normal clearance of P. aeruginosa and increase susceptibility to keratitis.
C57BL/6 mice were injected (sc) with scopolamine (50 µg) t.i.d. for 5 d with continuous exposure to air drafts of low humidity (< 40%). Control animals received PBS injections and were housed under vivarium standards. Tear production was measured with cotton threads, and corneal epithelium integrity assessed with fluorescein. After induction of dry eye, mice were topically inoculated with 109 CFU of invasive (strain PA01) or cytotoxic (strain 6206) P. aeruginosa without the introduction of a scratch-injury. Anesthesia was maintained for 1 or 3 h post-inoculation. Bacterial CFUs in tear fluid and on the ocular surface were quantified after 6 h. Bacterial adherence to, and traversal of, the corneal epithelium were evaluated after 9 h using 2-photon/confocal microscopy. Overall corneal health was monitored for up to 3 d after inoculation.
Dry eye mice showed reduced tear volumes after 5 d (25% of controls, p = 0.01, Mann-Whitney), but no fluorescein staining. With 1 h post-inoculation anesthesia, there was no difference between dry eye mice and controls in bacterial numbers in the tear fluid at 6 h. In contrast, 3 h post-inoculation anesthesia resulted in significantly fewer culturable bacteria from tears of dry eye mice (< 2% of controls, p = 0.0004, Mann-Whitney). Irrespective of anesthesia length, there was no difference between dry eye mice and controls regarding bacterial adherence to, or traversal of, the corneal epithelium. Neither the invasive nor cytotoxic strain caused visible pathology in dry or control eyes.
Induction of dry eye conditions in this model did not compromise normal ocular clearance of P. aeruginosa, nor did it increase susceptibility to infection. Indeed, dry eyes showed an enhanced capacity to clear bacteria under certain circumstances. These data show that decreased tear volume alone does not necessarily enable susceptibility to infection. It has yet to be determined what concurrent ocular surface alteration is necessary to increase infectivity.
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