Abstract
Purpose:
Smallpox virus is a significant bioweapon threat and vaccination has been reinstated for certain groups. Vaccinia keratitis (VK) following vaccination is a serious vision threat but little or nothing is known about the pathology of the disease. We previously developed a rabbit model of VK. The goal was to develop a mouse model that will facilitate studies on the pathology and immunology of VK.
Methods:
Scarified corneas of C57BL/6 and Balb/c female mice (4-6 weeks old) were infected with 10(5), 10(6) or 10(7) PFU of Dryvax or Vaccinia WR strain. Ocular disease severity (blepharitis, corneal neovascularization and stromal keratitis) was scored and tear film titers were taken every other day for 15 days. One-year-old female mice were also infected with 10(7) PFU of the WR strain to determine if there were any differences in disease severity due to age. Eyes were taken at each scoring day and sectioned for histopathology analysis and immunohistochemistry to analyze immune cell infiltration.
Results:
The Vaccinia Dryvax strain was highly attenuated, showing very little or no ocular disease in either strain of mouse. C57BL/6 mice infected with 10(7) PFU of Vaccinia strain WR had significantly higher stromal keratitis disease scores and titer values than Balb/c mice. Titers peaked on day 5 at 7.5 x 10(5) and 7.7 x 10(4) PFU/ml for C57BL/6 and Balb/c, respectively (p < 0.05). Mean peak stromal disease scores were 2.6 and 1.4 (p < 0.05), respectively for C57BL/6 and Balb/c mice. Infection with lower PFU of virus produced less severe disease and lower viral titers, thus 10(7) PFU was the optimal inoculum. There was no difference in disease scores or titers between 1-year-old and 6-week-old C57BL/6 mice. Histopathological analysis showed inflammatory cell (neutrophil, macrophage, lymphocyte) infiltration into the peripheral cornea and corneal edema.
Conclusions:
Ocular disease progression in the mouse depends on the strain of the mouse and strain of the virus. C57BL/6 mice are more susceptible to Vaccinia WR and Balb/c mice are resistant, which is the opposite of HSV-1. Mice are also significantly more resistant to VK than rabbits. This mouse model of Vaccinia keratitis will be useful for further studies of the disease.
Keywords: 573 keratitis •
480 cornea: basic science •
594 microbial pathogenesis: experimental studies