July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018

Axonal protection by a small molecule SIRT1 activator, SRT2104, with alteration of autophagy in optic nerve degeneration
Author Affiliations & Notes
  • Yasushi Kitaoka
    Ophthalmology, St Marianna Univ School of Med, Kawasaki, KANAGAWA, Japan
    Molecular Neuroscience, St. Marianna University Graduate School of Medicine, Kawasaki, Japan
  • Kana Sase
    Ophthalmology, St Marianna Univ School of Med, Kawasaki, KANAGAWA, Japan
  • Chihiro Tsukahara
    Ophthalmology, St Marianna Univ School of Med, Kawasaki, KANAGAWA, Japan
    Molecular Neuroscience, St. Marianna University Graduate School of Medicine, Kawasaki, Japan
  • Hitoshi Takagi
    Ophthalmology, St Marianna Univ School of Med, Kawasaki, KANAGAWA, Japan
  • Footnotes
    Commercial Relationships   Yasushi Kitaoka, None; Kana Sase, None; Chihiro Tsukahara, None; Hitoshi Takagi, None
  • Footnotes
    Support  KAKENHI 15K10908
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 623. doi:
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      Yasushi Kitaoka, Kana Sase, Chihiro Tsukahara, Hitoshi Takagi;
      Axonal protection by a small molecule SIRT1 activator, SRT2104, with alteration of autophagy in optic nerve degeneration
      . Invest. Ophthalmol. Vis. Sci. 2018;59(9):623.

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

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Abstract

Purpose :
To examine the effects of SRT2104, a SIRT1 activator, in optic nerve degeneration induced by TNF and to investigate whether it affects autophagic status after the induction of axonal degeneration.

Methods : Adult male Wistar rats were received intravitreal injection of TNF alone, concomitant injection of SRT2104 and TNF, or SRT2104 alone. Autophagic status in optic nerves was evaluated to examine p62 and LC3-II expression by immunoblot analysis. The effect of SRT2104 on TNF-induced axon loss was determined by counting the number of axons.

Results : Intravitreal injection of SRT2104 showed a modest protective tendency in the 2 pmol-treated groups against TNF-induced axon loss, although quantitative analysis showed no statistically significant (p = 0.0834 vs. TNF alone). However, significant protective effects were found in the 20 and 200 pmol-treated groups. SRT2104 alone injection significantly decreased p62 levels and increased LC3-II levels compared with the basal levels. Similarly, concomitant injection of SRT2104 and TNF significantly decreased p62 levels and increased LC3-II levels compared with the TNF-treated group.

Conclusions : The SIRT1 activator, SRT2104, exerts axonal protection in TNF-induced optic nerve degeneration. This effect may be associated with upregulated autophagic status in optic nerves.

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

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