title: Local ischemia and increased expression of vascular endothelial growth factor following ocular dissemination of Mycobacterium tuberculosis.
abstract: The pathogenesis of intraocular tuberculosis remains poorly understood partly due to the lack of adequate animal models that accurately simulate human disease. Using a recently developed model of ocular tuberculosis following aerosol infection of guinea pigs with Mycobacterium tuberculosis, we studied the microbiological, histological, and clinical features of intraocular tuberculosis infection. Viable tubercle bacilli were cultivated from all eyes by Day 56 after aerosol delivery of ∼200 bacilli to guinea pig lungs. Choroidal tuberculous granulomas showed reduced oxygen tension, as evidenced by staining with the hypoxia-specific probe pimonidazole, and expression of vascular endothelial growth factor (VEGF) was detected in the retinal pigment epithelium (RPE) and photoreceptors. Fundoscopic examination of M. tuberculosis-infected guinea pig eyes revealed altered vascular architecture and chorioretinal hemorrhage by Day 56 after infection. This model may be useful in further elucidating the pathogenesis of ocular tuberculosis, as well as in developing tools for diagnosis and assessment of antituberculosis treatment responses in the eye.
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Seema M
authors.initials: SM
authors.lastname: Thayil
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Albini
authors.forename: Hossein
authors.initials: H
authors.lastname: Nazari
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Moshfeghi
authors.forename: Jean-Marie A
authors.initials: JM
authors.lastname: Parel
authors.forename: Narsing A
authors.initials: NA
authors.lastname: Rao
authors.forename: Petros C
authors.initials: PC
authors.lastname: Karakousis
mesh_terms: D000336:Aerosols / Q000378:metabolism; D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology; D005123:Eye / Q000378:metabolism*; D015817:Eye Infections / Q000382:microbiology*; D005260:Female; D005786:Gene Expression Regulation; D006168:Guinea Pigs; D000860:Hypoxia; D007150:Immunohistochemistry / Q000379:methods; D007511:Ischemia; D008168:Lung / Q000382:microbiology; D008954:Models, Biological; D012160:Retina / Q000382:microbiology / Q000502:physiology; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D014376:Tuberculosis / Q000378:metabolism* / Q000382:microbiology*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D000336:Aerosols; D000995:Antitubercular Agents; D042461:Vascular Endothelial Growth Factor A