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Investigation of tissue cysts in the retina in a mouse model of ocular toxoplasmosis: distribution and interaction with glial cells

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Abstract

The conversion of tachyzoites into bradyzoites is a way for Toxoplasma gondii to establish a chronic and asymptomatic infection and achieve lifelong persistence in the host. The bradyzoites form tissue cysts in the retina, but not much is known about the horizontal distribution of the cysts or their interactions with glial cells in the retina. A chronic ocular toxoplasmosis model was induced by per oral administration of T. gondii Me49 strain cysts to BALB/c mice. Two months after the infection, retinas were flat-mounted and immunostained to detect cysts, ganglion cells, Müller cells, astrocytes, and microglial cells, followed by observation under fluorescence and confocal microscope. The horizontal distribution showed a rather clustered pattern, but the clusters were not restricted to certain location of the retina. Axial distribution was confined to the inner retina, mostly in ganglion cell layer or the inner plexiform layer. Both ganglion cells, a type of retinal neurons, and Müller cells, predominant retinal glial cells, could harbor cysts. The cysts were spatially separated from astrocytes, the most abundant glial cells in the ganglion cell layer, while close spatial distribution of microglial cells was observed in two thirds of retinal cysts. In this study, we demonstrated that the retinal cysts were not evenly distributed horizontally and were confined to the inner retina axially. Both neurons and one type of glial cells could harbor cysts, and topographic analysis of other glial cells suggests role of microglial cells in chronic ocular toxoplasmosis.

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Acknowledgements

This article is based on the doctoral dissertation of the first author (Song 2017), completed under the supervision of the corresponding author (JHK) at Seoul National University. This study was supported by Seoul National University Hospital Research Grant (04-2015-0270), the Bio & Medical Technology Development Program of the National Research Foundation funded by the Korean government, MSIP (2015M3A9E6028949), and the Development of Platform Technology for Innovative Medical Measurements Program from the Korea Research Institute of Standards and Science (KRISS-2017-GP2017-0020).

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Correspondence to Jeong Hun Kim.

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All animal experiments were approved by the Institutional Animal Care and Use Committee of Seoul National University and were conducted in agreement with the ARVO statement for the Use of Animals in Ophthalmic and Vision Research.

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Section Editor: Daniel K Howe

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Song, H.B., Jung, BK., Kim, J.H. et al. Investigation of tissue cysts in the retina in a mouse model of ocular toxoplasmosis: distribution and interaction with glial cells. Parasitol Res 117, 2597–2605 (2018). https://doi.org/10.1007/s00436-018-5950-3

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