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A. Kumar, J. Brown, F.-S. Yu; Cathelicidin, a Determinant Factor for Susceptibility Towards Bacterial Keratitis and Endophthalmitis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3901.
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Our previous studies implied a role of CRAMP in corneal and retinal innate immunity against bacterial pathogens. In the present study, we assessed the role of CRAMP in the eye by determining the susceptibility of CRAMP deficient (Cnlp-/-) mice to Pseudomonas aeruginosa (PA) keratitis and Staphylococcus aureus (SA) endophthalmitis.
Pseudomonas Keratitis was induced by inoculation of ATCC 19660 strain of PA on needle injured corneas of wild type (C57BL/6) and Cnlp-/- mice (B6 background) and endophthalmitis was induced by intravitreal injection SA (RN6390 strain). The disease response was graded on different days post infection (dpi) by an ophthalmologist in a blinded fashion using dissection, slit lamp and fundus microscopes. Susceptibility of WT and Cnlp-/- mice was assessed by determining the number of bacteria required to cause infection and by the severity of the diseases. The corneas or whole retinas were also subjected to histopathological analysis, bacterial load, myeloperoxidase (MPO) assay to determine neutrophil infiltration and ELISA for cytokine production.
Compare to WT, the Cnlp-/- mice showed increased susceptibility to PA keratitis as 10 times less bacteria were sufficient to cause infection in 100% of Cnlp-/- mice (103 versus 104 cfu in WT mice). Moreover, when same inoculum (104 cfu/cornea) was used, the disease progressed much faster in Cnlp-/- mice and their corneas perforated within three days (5 days in the control mice). Furthermore, the Cnlp-/- mice showed significant higher (8 fold) bacterial burden, much higher cytokines expression and PMN infiltration in Cnlp-/-mice compared to the wild-type controls. Intravitreal injection of both 500 and 5000 cfu of SA induced the inflammatory response in WT and Cnlp-/- mice at 1 dpi. At 3 dpi, while only the mice infected with 5000 cfu of SA showed sign of endophthalmitis in WT mice, both inoculums caused inflammation in Cnlp-/- mice.
CRAMP-deficient mice showed increased susceptibility to bacterial keratitis and endophthalmitis. Antimicrobial peptide CRAMP plays an important role in innate defense of the eye.
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