Experimental ocular tuberculosis in guinea pigs.
OBJECTIVE
To develop an animal model of intraocular tuberculosis (TB) with features of pulmonary TB and extrapulmonary dissemination to the eye.


METHODS
Hartley strain guinea pigs were infected via an aerosol route with virulent Mycobacterium tuberculosis. One group of guinea pigs was infected with a relatively low bacterial inoculum and received no treatment. A second group of guinea pigs received high-dose infection and were treated with the first-line anti-TB drugs isoniazid, rifampin, and pyrazinamide. Development of ocular TB lesions was documented by histological analysis, acid-fast staining, and real-time polymerase chain reaction for M tuberculosis DNA.


RESULTS
Untreated guinea pigs developed pulmonary and extrapulmonary TB. Ocular TB, primarily involving the uvea, developed in 5 of 12 eyes (42%). Uveal granulomatous lesions showed the presence of acid-fast organisms and M tuberculosis DNA. In treated animals, none of the 8 eyes examined revealed the presence of acid-fast organisms; however, there was mild nongranulomatous uveitis in 4 eyes.


CONCLUSIONS
Mycobacterium tuberculosis delivered via aerosol to guinea pigs results in extrapulmonary dissemination to the eye. Of significance, intraocular changes in this model include granulomatous inflammation and the presence of acid-fast organisms, as seen in human cases of ocular TB. Clinical Relevance 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.
Rao
Narsing A
NA
Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Albini
Thomas A
TA
Kumaradas
Mirnalini
M
Pinn
Michael L
ML
Fraig
Mostafa M
MM
Karakousis
Petros C
PC
D000336:Aerosols; D000818:Animals; D000995:Antitubercular Agents / Q000627:therapeutic use; D004269:DNA, Bacterial / Q000032:analysis; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007538:Isoniazid / Q000627:therapeutic use; D008168:Lung / Q000382:microbiology / Q000473:pathology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D016133:Polymerase Chain Reaction; D011718:Pyrazinamide / Q000627:therapeutic use; D012293:Rifampin / Q000627:therapeutic use; D013154:Spleen / Q000382:microbiology; D014392:Tuberculosis, Ocular / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology
D000336:Aerosols; D000995:Antitubercular Agents; D004269:DNA, Bacterial; D011718:Pyrazinamide; D007538:Isoniazid; D012293:Rifampin