Experimental Ocular Tuberculosis in Guinea Pigs

Rao, Narsing A.; Albini, Thomas A.; Kumaradas, M.; Pinn, Michael L.; Fraig, Mostafa; Karakousis, Petros C.

doi:10.1001/archophthalmol.2009.220

Cited by 43 publications

(27 citation statements)

References 23 publications

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“…6 An animal model of ocular TB in aerosol-infected guinea pigs has demonstrated the development of ocular lesions from lung infection, although it provides limited information on immune mechanisms in human disease. 7 Despite these developments, several clinical observations that are crucial to the diagnosis and management of TBU remain unexplained. These include the strong inflammatory response in TBU despite its paucibacillary nature, need for adjunct corticosteroid therapy in most cases, and anecdotal evidence of resolution of ocular lesions without anti-TB therapy.…”

mentioning

confidence: 99%

Autoreactive T Cells in Immunopathogenesis of TB-Associated Uveitis

Tagirasa

Parmar

Barik

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Intraocular inflammation in tuberculosis-associated uveitis (TBU) is usually widespread, and responds unpredictably to treatment. Herein, we analyze the intraocular Tcell response in TBU for its surface phenotype, antigenic specificity, and functional characteristics to explain the above observations. METHODS. We isolated T cells from vitreous humor samples of patients with TBU and non-TB uveitis (controls). These were directly stained for surface markers CD4, CD8, CD45RO, CD45RA, CCR7, as well as intracellular cytokines IFN-c, TNF-a, and IL-17 and analyzed on flow cytometry. Antigenic specificity was determined by activating with Mycobacterium tuberculosis-specific antigen Early Secreted Antigenic Target-6 (ESAT-6) or retinal crude extract (RCE). Activation-induced cell death (AICD) characteristics of each T-cell population were analyzed by staining for PI-Annexin V, Fas-FasL, phospho-Akt, and phospho-Erk1/2. RESULTS. Immunophenotyping of vitreous humor samples demonstrated polyfunctional effector and central memory CD4þ T helper cells coexpressing IFN-c, TNF-a, and IL-17. Both ESAT-6 and RCE (autoreactive) specificity was found in T cells extracted from TBU samples; however, the mycobacterial and autoreactive T-cell populations differed in their sensitivity to AICD. Autoreactive T cells appeared to resist AICD through decreased expression of apoptotic markers, FasL and caspase-3, sustained phosphorylation of Akt, and lowered Erk1/2 activity.CONCLUSIONS. Autoreactive T cells are present in TBU eyes and are relatively resistant to AICD. An understanding of this epiphenomenon could be crucial in planning treatment of TBU patients, and interpreting response to anti-TB therapy.

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mentioning

confidence: 99%

Autoreactive T Cells in Immunopathogenesis of TB-Associated Uveitis

Tagirasa

Parmar

Barik

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…Rao et al 12 developed an experimental guinea pig model to understand the pathogenesis of ocular tuberculosis and to reproduce natural route of infection through lungs. Their observations indicate that guinea pigs when infected with M. tuberculosis via an aerosol route showed development of pulmonary TB in all animals and ocular lesions developed in 42%.…”

Section: Pathogenesis Of Ocular Tbmentioning

confidence: 99%

“…This model reiterates the belief that intraocular TB results from hematogenous spread from the primary complex or from post primary reactivated lung lesions. 12 Bacilli in the ocular tissue, as in other extrapulmonary sites, may remain dormant in RPE for years before they are activated.…”

Section: Pathogenesis Of Ocular Tbmentioning

confidence: 99%

Intraocular Tuberculosis

Parchand¹,

Gupta²

2013

Journal of Postgraduate Medicine, Education and Research

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Intraocular tuberculosis remains a major diagnostic challenge and it is extremely important to establish the diagnosis as the specific treatment helps in reducing the recurrences, thus reducing ocular morbidity. The present review aims to describe the global epidemiology and pathogenesis of intraocular tuberculosis with clinical spectrum and different presentations. The challenges in establishing the diagnosis with role of conventional tests like PPD skin test as well as current diagnostic tests including interferon gamma release assay and molecular diagnostic tests are discussed. The treatment requires anti-tuberculosis therapy with the use of concomitant corticosteroids and carries good prognosis provided the treatment is started in the early stage.

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“…The neuropathy is usually reversible, but complete recovery may take several months. [ 51 ] have recently used Hartley strain guinea pigs that were infected via an aerosol route. Some animals were infected with low doses of bacteria and were merely observed.…”

Section: Ocular Toxicity In Antitubercular Therapymentioning

confidence: 99%

Retinal and Choroidal Manifestations of Tuberculosis

Mehta

Banker²,

Chauhan³

2012

Retinal and Choroidal Manifestations of Selected Systemic Diseases

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Ocular tuberculosis has been recognized from the nineteenth century onward due to the work of Gueneau de Mussy, Jaeger, Fraenkel, and Bouchut. Ocular tuberculosis had a high prevalence worldwide in the twentieth century, but this prevalence has reduced signi fi cantly in the western hemisphere, a decline that has paralleled the decline of tuberculosis as a common systemic infection. In recent times, the prevalence varies from 18% (Spain) to 1.39% (India). The advent of the human immunode fi ciency virus (HIV) epidemic has led to an increase in the prevalence of ocular tuberculosis to up to 23.5%. Manifestations vary depending upon the ocular tissue involved. The manifestations can either be due to direct tissue infection or be hypersensitivity reactions. Rare manifestations include the eyelids (lupus vulgaris), the conjunctiva (conjunctivitis), cornea (ulcers and phlyctenulosis), and the sclera (scleritis). The most common manifestations include uveal involvement in the form of tubercles, tuberculomas, and serpiginous-like choroiditis. Other manifestations include orbital apex syndrome and lesions associated with neurotuberculosis (disc edema and sixth nerve palsies). The diagnostic workup of patients with suspected ocular tuberculosis has both systemic and ocular components. The systemic investigations include (1) radiography: (a) chest X-rays and computed tomography of the chest and (b) abdominal CT scan or ultrasonography; (2) Mantoux testing; and (3) interferon-g (gamma) release assays (IGRA). Ocular investigations of ocular fl uids or tissue biopsies include (1) microscopy, (2) culture, and (3) PCR (polymerase chain reaction) techniques. The treatment includes the use of topical, periocular, or systemic corticosteroids with a four-drug regimen of antitubercular therapy.

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Experimental Ocular Tuberculosis in Guinea Pigs

Cited by 43 publications

References 23 publications

Autoreactive T Cells in Immunopathogenesis of TB-Associated Uveitis

Autoreactive T Cells in Immunopathogenesis of TB-Associated Uveitis

Intraocular Tuberculosis

Retinal and Choroidal Manifestations of Tuberculosis

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