September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Disruption of outer blood retinal barrier by Toxoplasma gondii-infected monocytes is mediated via FAK signaling pathway
Author Affiliations & Notes
  • Hyun Beom Song
    Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea (the Republic of)
    Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea (the Republic of)
  • Hyoung Oh Jun
    Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea (the Republic of)
  • Jin Hyoung Kim
    Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea (the Republic of)
  • Sang-Mok Lee
    Department of Ophthalmology, Hallym University Sacred Heart Hospital, Anyang, Korea (the Republic of)
  • Jiwon Shim
    Department of Life Sciences, College of Natural Science, Hanyang University, Seoul, Korea (the Republic of)
  • Min-Ho Choi
    Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Jeong Hun Kim
    Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea (the Republic of)
    Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea (the Republic of)
  • Footnotes
    Commercial Relationships   Hyun Beom Song, None; Hyoung Oh Jun, None; Jin Hyoung Kim, None; Sang-Mok Lee, None; Jiwon Shim, None; Min-Ho Choi, None; Jeong Hun Kim, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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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. 201657(12):.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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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