Murine model of primary acquired ocular toxoplasmosis: Fluorescein angiography and multiplex immune mediator profiles in the aqueous humor

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Abstract

PURPOSE. To establish a murine model of primary acquired ocular toxoplasmosis (OT) and to investigate the immune mediator profiles in the aqueous humor (AH). METHODS. C57BL/6 mice were perorally infected with Toxoplasma gondii. The ocular fundus was observed, and fluorescein angiography (FA) was performed. The AH, cerebrospinal fluid (CSF), and serum were collected before infection and at 28 days postinfection (dpi); the immune mediator levels in these samples were analyzed using multiplex bead assay. RESULTS. Fundus imaging revealed soft retinochoroidal lesions at 14 dpi; many of these lesions became harder by 28 dpi. FA abnormalities, such as leakage from retinal vessels and dilation and tortuosity of the retinal veins, were observed at 14 dpi. Nearly all these abnormalities resolved spontaneously at 28 dpi. In the AH, interferon-γ, interleukin (IL)-1α, IL-1β, IL-6, IL-10, IL-12(p40), IL-12(p70), CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES, and CXCL1/KC levels increased after infection. All these molecules except IL-1α, IL-4, and IL-13 showed almost the same postinfection patterns in the CSF as they did in the AH. The tumor necrosis factor α, IL-4, and IL-5 levels in the AH and CSF of the T. gondii-infected mice were lower than those in the serum. The postinfection IL-1α, IL-6, CCL2/MCP-1, CCL4/MIP-1β, and granulocyte colony-stimulating factor levels in the AH were significantly higher than those in the CSF and serum. CONCLUSIONS. A murine model of primary acquired OT induced via the natural infection route was established. This OT model allows detailed ophthalmologic, histopathologic, and immunologic evaluations of human OT. Investigation of AH immune modulators provides new insight into OT immunopathogenesis.

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Li, K., Feng, X., Hikosaka, K., & Norose, K. (2021). Murine model of primary acquired ocular toxoplasmosis: Fluorescein angiography and multiplex immune mediator profiles in the aqueous humor. Investigative Ophthalmology and Visual Science, 62(3). https://doi.org/10.1167/IOVS.62.3.9

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