June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
The breakdown of tight junction in retinal pigment epithelium by Aβ via RAGE signaling pathway
Author Affiliations & Notes
  • Chung Young Kim
    Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Hospital , Seoul , Seoul, Korea (the Republic of)
  • Sung Wook Park
    Fight against Angiogenesis-Related Blindness 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 Laboratory, Biomedical Research Institute , Seoul National University Hospital, Seoul, Korea (the Republic of)
  • Jin Hyoung Kim
    Fight against Angiogenesis-Related Blindness Laboratory, Biomedical Research Institute , Seoul National University Hospital, Seoul, Korea (the Republic of)
  • Jeong Hun Kim
    Fight against Angiogenesis-Related Blindness 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   Chung Young Kim, None; Sung Wook Park, None; Hyoung-Oh Jun, None; Jin Hyoung Kim, None; Jeong Hun Kim, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5236. doi:
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    • Get Citation

      Chung Young Kim, Sung Wook Park, Hyoung-Oh Jun, Jin Hyoung Kim, Jeong Hun Kim; The breakdown of tight junction in retinal pigment epithelium by Aβ via RAGE signaling pathway. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5236.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Amyloid beta (Aβ) has been implicated in the pathogenesis of age-related macular degeneration (AMD). Although Aβ is predominantly secreted from the neuronal cells, the mechanism how extracellular Aβ decrease tight junction in RPE remain to be fully elucidated. This study is aimed to demonstrate the role of receptor for advanced glycation end products (RAGE) signaling pathway in Aβ induced breakdown of tight junction in RPE.

Methods : To evaluate in vivo effect of exogenous Aβ on tight junction in RPE, subretinal injection of Aβ42 or PBS was performed in C57BL/6J mice. Then, Aβ and ZO-1 were evaluated in RPE/choroid/scleral complex. Using immunocytochemistry and western blot, we determined the signaling pathway after Aβ42 treatment in ARPE-19 cells. We also evaluate the effect of RAGE siRNA and NF-Kb inhibitor in Aβ induced tight junction breakdown. To determine the role of RAGE signaling in vivo, we evaluated tight junction after Aβ treatment with NF-Kb inhibitor.

Results : Aβ induced breakdown of tight junction in the RPE after subretinal injection of Aβ into the mouse eye. We also presented evidence that various downstream signaling of RAGE was activated by Aβ in the RPE. siRNA mediated RAGE knockdown or NF-KB inhibitor prevented tight junction breakdown in RPE. Blockade of NF-Kb protected Aβ induced breakdown of tight junction in RPE.

Conclusions : Our data demonstrates that Aβ activated RAGE signaling pathway and induced breakdown of tight junction in RPE. Thus, we suggest that RAGE could be a potential therapeutic target for Aβ induced outer BRB breakdown in AMD.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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