Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
PLoS One. 2011;6(12):e28383. doi: 10.1371/journal.pone.0028383. Epub 2011 Dec 5.
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.
眼内结核的发病机制仍不完全清楚，部分原因是缺乏能够准确模拟人类疾病的足够的动物模型。本研究使用最近开发的豚鼠雾化感染结核分枝杆菌的眼部结核模型，研究了眼内结核感染的微生物学、组织学和临床特征。在豚鼠肺部雾化输送约 200 个结核分枝杆菌细菌后第 56 天，所有眼睛均通过培养分离出活的结核分枝杆菌。用缺氧特异性探针 pimonidazole 染色证实脉络膜结核性肉芽肿的氧张力降低，并且在视网膜色素上皮（RPE）和光感受器中检测到血管内皮生长因子（VEGF）的表达。在感染后第 56 天，对 M. tuberculosis 感染的豚鼠眼睛进行眼底检查，发现血管结构改变和脉络膜视网膜出血。该模型可能有助于进一步阐明眼内结核的发病机制，以及开发用于眼部结核诊断和评估抗结核治疗反应的工具。
