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Hyun Beom Song, Hyoung Oh Jun, Jin Hyoung Kim, Sang-Mok Lee, Jiwon Shim, Min-Ho Choi, Jeong Hun Kim; Disruption of outer blood retinal barrier by Toxoplasma gondii-infected monocytes is mediated via FAK signaling pathway. Invest. Ophthalmol. Vis. Sci. 2016;57(12):No Pagination Specified. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
In patients with ocular toxoplasmosis, disruption of retinal pigment epithelium is frequently observed. The retinal pigment epithelial layer constitutes outer blood retinal barrier (BRB) that lies between retina and leaky choroidal vasculature. In this study, we investigated the effect of monocytes infected with Toxoplasma gondii on in vitro model of outer BRB.
Retinal pigment epithelial cells, ARPE-19, were cultivated on transwell to form a confluent monolayer. Then, human monocytic cells, THP-1, infected with Toxoplasma gondii or their conditioned medium were treated and the barrier function was evaluated by measurement of transepithelial electrical resistance (TEER) and immunocytochemistry of tight junction proteins. Additional treatment with FAK inhibitor (PF-573228) or neutralizing antibody against IL-8 was performed to investigate the associated signaling pathway.
Twenty-four hours after the treatment with infected monocytes or their conditioned medium, TEER was decreased and tight junction protein was disrupted. Interestingly, additional treatment with FAK inhibitor attenuated the decreased TEER and disrupted tight junction protein induced by the conditioned medium. After demonstrating increased concentration of IL-8 in conditioned medium from infected monocytes, we found additional treatment with neutralizing antibody against IL-8 could decrease phosphorylation of FAK and attenuate the decreased TEER and the disrupted tight junction protein.
Monocytes infected with Toxoplasma gondii can impair outer BRB. The paracrine effects of infected monocytes on outer BRB are mediated via FAK signaling that is activated by IL-8 from monocytes.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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