Abstract
Purpose: :
To study ocular TB pathogenesis in a highly relevant animal model.
Methods: :
Hartley strain guinea pigs were infected via low-dose aerosol with Mycobacterium tuberculosis CDC1551. Ocular pathology was documented by histological exam, mycobacterial culture, acid-fast staining, quantitative PCR for M. tuberculosis DNA, and fundus photography. Immunohistochemistry was performed using monoclonal antibodies against the hypoxia-specific probe pimonidazole and vascular endothelial growth factor (VEGF).
Results: :
Ocular TB primarily involving the uvea developed in all animals. By Day 56 after infection, fundoscopic examination of animals infected with low-dose aerosol revealed altered vascularization and chorioretinal hemorrhage, and viable bacilli were cultivated from all eyes, despite negative acid-fast staining and M. tuberculosis PCR. Choroidal tuberculous granulomas showed reduced oxygen tension and VEGF expression was detected in the retinal pigment epithelium and photoreceptors.
Conclusions: :
This model may be useful in elucidating the pathogenesis of ocular TB, as well as in developing tools for diagnosis and assessment of anti-TB treatment responses in the eye.
Keywords: uveitis-clinical/animal model • hypoxia • immunohistochemistry