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T. A. Albini, P. C. Karakousis, M. Kumaradas, M. L. Pinn, M. M. Fraig, N. A. Rao; Experimental Ocular Tuberculosis in Guinea Pigs. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3458.
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The pathogenesis of intraocular tuberculosis (TB) remains poorly understood partly due to the lack of adequate animal models that accurately simulate human disease. We describe an animal model of intraocular TB with histologic features of pulmonary TB and extrapulmonary dissemination similar to human cases of intraocular TB.
Hartley strain guinea pigs were infected via aerosol with virulent Mycobacterium tuberculosis strain CDC1551 or H37Rv using the Inhalation Exposure System (Glas-Col, Terre Haute, IN). Six guinea pigs were infected with a relatively low bacterial inoculum and received no treatment, and a second group of six guinea pigs received high dose infection and were treated with the first-line anti-TB drugs isoniazid, rifampin, and pyrazinamide. Development of pulmonary TB with dissemination was determined by microbiological examination of lung and spleen tissues. Development of ocular TB lesions was documented by histology, acid-fast staining, and real-time PCR for M. tuberculosis DNA.
Untreated guinea pigs developed progressive pulmonary and extrapulmonary TB. Ocular tuberculosis developed in 41% of the eyes of these animals, primarily involving the uvea. Of the twelve untreated guinea pig eyes examined, four eyes showed uveal involvement and one eye revealed a granuloma involving the limbus. Quantitative PCR was positive for Mtb DNA in three eyes with uveal involvement and in the eye with the limbal granuloma. Two of the five ocular TB granulomas were positive by acid-fast staining.
M. tuberculosis delivered via aerosol to guinea pigs results in development of pulmonary TB, as well as extrapulmonary dissemination to the eye. Importantly, intraocular changes in this model include granulomatous choroiditis as seen in human cases of ocular TB. Systematic investigation using the guinea pig model may provide greater insight into the pathogenesis of intraocular TB and assist in the development of novel modalities to treat this global infectious disease.
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