IOVS Journal of Experimental Medicine
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(Investigative Ophthalmology and Visual Science. 2007;48:781-788.)
© 2007 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.06-1036
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Adenovirus Type 37 Keratitis in the C57BL/6J Mouse

Ashish V. Chintakuntlawar,1,2 Roger Astley,1 and James Chodosh1,2,3

From the Molecular Pathogenesis of Eye Infection Research Center, Dean A. McGee Eye Institute, and the 1Departments of Ophthalmology, 2Cell Biology, and 3Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.

PURPOSE. To develop a mouse model of adenoviral keratitis that will allow further study of viral and host pathogenic mechanisms.

METHODS. Corneas of C57BL/6J mice were injected with adenovirus type 37 (Ad37) or virus-free dialysis buffer by a gas-powered microinjection system coupled to a glass micropipette needle. Mouse corneas were examined for signs of inflammation, by clinical examination, immunohistochemistry, and confocal microscopy; assayed for viral and chemokine mRNA expression by real-time PCR; titered to assess viral replication; and subjected to ELISA for chemokine and myeloperoxidase (MPO) protein expression.

RESULTS. C57BL/6J mice corneas injected with 105 TCID (tissue culture infective dose) Ad37 showed stromal opacification and inflammation beginning from 1 day after injection and continuing for several months, while buffer-injected corneas showed no signs of inflammation. Ad37-injected corneas expressed adenoviral E1A 10S and E1B 19k mRNA but not IIIa, and viral titers had fallen two logs by day 4 after injection. When compared to untouched and buffer-injected corneas, Ad37-injected corneas expressed significantly higher levels of IL-6, KC, and MCP-1 mRNA at 4 hours after injection (P < 0.05). By ELISA, KC protein was significantly elevated in Ad37-injected corneas at 8 and 16 hours, and MCP-1 protein at 16 hours after injection (P < 0.05). Ad37-injected corneas showed elevated levels of MPO (P = 0.0024) at 4 days after injection consistent with immunohistochemical evidence for a predominance of neutrophils in the corneal stroma.

CONCLUSIONS. Ad37 induces an acute immunopathologic response in the C57BL/6J mouse cornea, despite an absence of viral replication. This new animal model of Ad37 keratitis will facilitate studies of the molecular pathogenesis of the disorder.




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Invest. Ophthalmol. Vis. Sci., October 1, 2008; 49(10): 4482 - 4489.
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