June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Aβ induced dysregulation of autophagy in retinal pigment epithelium contributes to the pathogenesis of dry age-related macular degeneration
Author Affiliations & Notes
  • Sung Wook Park
    FARB, Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea (the Republic of)
    Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Hyoung-Oh Jun
    FARB, Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea (the Republic of)
  • Jin Hyoung Kim
    FARB, Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea (the Republic of)
  • Byung Joo Lee
    FARB, Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea (the Republic of)
    Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Kihwang Lee
    Ophthalmology, Ajou University School of Medicine, Seongnam-si, Korea (the Republic of)
  • Woo Jin Park
    Life Sciences Concentration GIST, Gwangju, Korea (the Republic of)
  • Jeong Hun Kim
    FARB, Department of Ophthalmology, Seoul National University Hospital, Seoul, Korea (the Republic of)
    Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea (the Republic of)
  • Footnotes
    Commercial Relationships   Sung Wook Park, None; Hyoung-Oh Jun, None; Jin Hyoung Kim, None; Byung Joo Lee, None; Kihwang Lee, None; Woo Jin Park, None; Jeong Hun Kim, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5239. doi:
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    • Get Citation

      Sung Wook Park, Hyoung-Oh Jun, Jin Hyoung Kim, Byung Joo Lee, Kihwang Lee, Woo Jin Park, Jeong Hun Kim; Aβ induced dysregulation of autophagy in retinal pigment epithelium contributes to the pathogenesis of dry age-related macular degeneration
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):5239.

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

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Abstract

Purpose : Intracellular amyloid beta (Aβ) in retinal pigment epithelium (RPE) has been implicated in the pathogenesis of age-related macular degeneration (AMD). This study is aimed to demonstrate that autophagic dysfunction by Aβ contributes to autophagic cell death in RPE as a possible pathogenesis of dry AMD.

Methods : After Aβ42 treatment in ARPE-19 cells, we evaluated cell viability and cell death mechanism by Western blot and immunocytochemistry. In addition, we performed an intravitreal injection of Aβ to induce dry AMD mouse model.

Results : Intracellular Aβ induced non-apoptotic cell death in a dose dependent manner. Dysfunction of autophagic flux by Aβ leaded to autophagic cell death. In addition, Aβ induced lysosomal depletion as well as mitochondrial depletion. Inhibition of Aβ uptake by blocking RAGE or enhancement of autophagic flux with rapamycin effectively rescued RPE from Aβ induced cell death. In vivo, intravitreal injection of Aβ induced autophagy and cell death. Rapamycin prevents Aβ induced RPE degeneration in mouse.

Conclusions : Aβ induced dysregulation of autophagy (lysosomal impairment) and autophagic cell death in retinal pigment epithelium. We suggested autophagic dysfunction by Aβ as a pathogenesis of dry 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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