Rao Narsing A, Albini Thomas A, Kumaradas Mirnalini, Pinn Michael L, Fraig Mostafa M, Karakousis Petros C
Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Arch Ophthalmol. 2009 Sep;127(9):1162-6. doi: 10.1001/archophthalmol.2009.220.
To develop an animal model of intraocular tuberculosis (TB) with features of pulmonary TB and extrapulmonary dissemination to the eye.
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.
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.
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.
建立一种具有肺结核特征并可经肺外播散至眼部的眼内结核动物模型。
采用气溶胶途径将强毒力结核分枝杆菌感染Hartley品系豚鼠。一组豚鼠感染相对低剂量的细菌且未接受治疗。另一组豚鼠接受高剂量感染,并接受一线抗结核药物异烟肼、利福平及吡嗪酰胺治疗。通过组织学分析、抗酸染色及结核分枝杆菌DNA的实时聚合酶链反应记录眼内结核病变的发展情况。
未治疗的豚鼠发生了肺结核和肺外结核。12只眼中有5只(42%)发生了主要累及葡萄膜的眼内结核。葡萄膜肉芽肿性病变显示存在抗酸菌及结核分枝杆菌DNA。在接受治疗的动物中,所检查的8只眼中均未发现抗酸菌;然而,有4只眼出现了轻度非肉芽肿性葡萄膜炎。
经气溶胶途径将结核分枝杆菌接种于豚鼠可导致肺外播散至眼部。重要的是,该模型中的眼内变化包括肉芽肿性炎症及抗酸菌的存在,这与人类眼内结核病例所见相同。临床意义 豚鼠模型可能有助于更深入了解眼内结核的发病机制,并有助于开发治疗这种全球感染性疾病的新方法。