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D.O. Girgis, G.D. Sloop, J.M. Reed, R.J. O'Callaghan; Susceptibility of Aged Mice to Staphylococcus aureus Keratitis . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1448.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine the effect of age on the pathogenesis of Staphylococcus keratitis employing a new model of corneal infection in three strains of mice. Methods: Corneas of young (6-7 weeks of age) and aged (9-12 months of age) mice (BALB/c, A/J, and C57BL/6) were scarified and topically inoculated with log phase S. aureus strain 8325-4. At various time points postinfection (PI), mice underwent slit lamp examination (SLE) and eyes were analyzed for histopathological changes. Whole eye homogenates were analyzed in triplicate for bacterial colony forming units (CFU) and myeloperoxidase (MPO) activity. Results: For young mice, moderate keratitis was observed in BALB/c and A/J mice by 5 days postinfection, but not in C57BL/6 mice. In contrast, all aged mice demonstrated mild to moderate signs of keratitis as soon as 1 day PI. BALB/c and A/J mice demonstrated severe keratitis by day 3, and as a result these infections were terminated at this time point. In contrast, C57BL/6 mice demonstrated mild to moderate keratitis from 3 to 9 days PI. SLE scores of infected eyes of all three strains of aged mice were significantly higher at days 1 and 3 PI as compared to infected eyes of young mice of each strain (P≤0.0001). Histopathological analysis revealed acute inflammation of the iris, ciliary body, and limbus, with inflammatory exudates observed in the anterior chamber as early as 1 day PI in aged mice, although these pathological changes were mildest in C57BL/6 mice. Adherence of neutrophils to the aspect of Descemet's membrane adjacent to the anterior chamber and migration into the cornea was identified. Neutrophil migration from the limbus to the central cornea was also observed. Conclusions: Aged mice of all three strains demonstrated an enhanced pathological response to S. aureus infection as compared to young mice of the same strains. Furthermore, the resistance to infection observed in young C57BL/6 mice was minimized in aged mice.
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