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F. X. Yu, A. Kumar, N. Gao; Topical Application of Flagellin Prevents the Development of Pseudomonas Aeruginosa Keratitis in Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6340.
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In the present study we sought to determine whether the topical application of flagellin exhibits protective effects on the development of Pseudomonas (P.) aeruginosa keratitis and to elucidate the underlying mechanisms.
Purified flagellin was topically applied on needle wounded wild type (B6) or cathelicidin related antimicrobial peptide (CRAMP) deficient (Cnlp-/-) mouse cornea. At various time points post flagellin application, the corneas were either harvested and assayed for expression of cytokines or subjected to P. aeruginosa (ATCC 19660 strain) infection. The corneal disease response was assessed by slit lamp microscopic examination, histopathological analysis, determination of bacterial load, cytokines/chemokine expression, and neutrophil infiltration to the cornea.
Topical application of flagellin 6 and 24 h prior to P. aeruginosa inoculation significantly improved disease outcome in wild-type B6 mice, preserved corneal structural integrity and transparency, and thus maintained vision in otherwise perforated corneas. Topical application of flagellin on wounded but not the intact cornea induced PMN infiltration and markedly up-regulated CRAMP expression. Deletion of CRAMP and depletion of PMN abolished flagellin-protection in B6 mice.
The topical application of flagellin on wounded cornea is very effective to prevent the development of keratitis and the induced expression of antimicrobial peptide CRAMP plays an important role in innate defense of the cornea.
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