July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Autophagy Activated by SIRT6 Regulates Amyloid-β Induced Inflammatory Response in RPEs
Author Affiliations & Notes
  • Xiaodong Sun
    Ophthalmology, Shanghai First Peoples Hospital, Shanghai, China
  • Xueting Luo
    Ophthalmology, Shanghai First Peoples Hospital, Shanghai, China
  • Yiji Feng
    Ophthalmology, Shanghai First Peoples Hospital, Shanghai, China
  • Jian Liang
    Ophthalmology, Shanghai First Peoples Hospital, Shanghai, China
  • Footnotes
    Commercial Relationships   Xiaodong Sun, None; Xueting Luo, None; Yiji Feng, None; Jian Liang, None
  • Footnotes
    Support   National Natural Science Foundation of China (81730026, 81700828, 81400413)
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4615. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Xiaodong Sun, Xueting Luo, Yiji Feng, Jian Liang; Autophagy Activated by SIRT6 Regulates Amyloid-β Induced Inflammatory Response in RPEs. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4615.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Age-associated dysfunction of retinal pigment epithelial cells (RPEs) is considered to be the initial trigger of retinal diseases such as age-related macular degeneration. Although autophagy is upregulated in RPEs during the course of aging, little is known about how autophagy is regulated and its functional role in RPEs. The purpose of this study is to determine whether Sirtuin 6 (SIRT6) contribute to regulation of autophagic and inflammatory pathways in RPEs.

Methods : Deposition of amyloid-β, and the levels of autophagy markers and SIRT6 were evaluated in the retinal sections of aging C57BL/6 mice. Two months old mice were intravitreally injected with amyloid-β1-40 at 14μg/5μL or PBS and the primary mouse RPEs were collected for examination of autophagy markers and inflammation cytokines. SIRT6 expression was inhibited using siRNA knockdown or overexpressed with plasmid transfection and the effects on expression of autophagy markers were measured by immunofluorescence and western blot. Autophagy activation was inhibited using 3-methyladenine (3-MA) and the effect on expression of inflammation cytokines was measured in with ARPE-19 cells treated after amyloid-β1-40.

Results : In this study, we found that expression of Sirtuin 6 (SIRT6) and autophagic markers are upregulated in RPEs of aged mice where subretinal deposition of amyloid-β is accumulated and in amyloid-β stimulated RPEs. In addition, gain and loss-of-function studies confirmed the positive role of SIRT6 in regulating autophagy. Interesting, inhibition of autophagy attenuates amyloid-β stimulated inflammatory response in RPEs.

Conclusions : Our findings uncover the autophagy modulated by SIRT6 may be a proinflammatory mechanism for amyloid-β induced RPE dysfunction.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×