September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Ripasudil, a ROCK inhibitor, modulates p62 expression in TNF-induced optic nerve degeneration
Author Affiliations & Notes
  • Yasushi Kitaoka
    Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Japan
    Molecular Neuroscience, St. Marianna University Graduate School of Medicine, Kawasaki, Japan
  • Kana Sase
    Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Japan
  • Yasunari Munemasa
    Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Japan
  • Hitoshi Takagi
    Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Japan
  • Footnotes
    Commercial Relationships   Yasushi Kitaoka, Kowa Company (R); Kana Sase, None; Yasunari Munemasa, None; Hitoshi Takagi, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5066. doi:
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    • Get Citation

      Yasushi Kitaoka, Kana Sase, Yasunari Munemasa, Hitoshi Takagi; Ripasudil, a ROCK inhibitor, modulates p62 expression in TNF-induced optic nerve degeneration
      . Invest. Ophthalmol. Vis. Sci. 2016;57(12):5066.

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

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Abstract

Purpose : Ripasudil, a ROCK inhibitor, has been shown to decrease intraocular pressure. However, its role in optic nerve axonal degeneration remains to be examined. Thus, we determined whether ripasudil modulates axonal loss induced by tumor necrosis factor (TNF) and affects the expression of p62, also called sequestosome 1, in TNF-induced optic nerve degeneration.

Methods : Experiments were performed on adult male Wistar rats that received an intravitreal injection of 10 ng TNF alone or simultaneous injection of TNF and 2, 20, or 200 pmol of ripasudil. The effects of ripasudil on axons were evaluated by morphometric analysis 2 weeks after intravitreal injection. The expression of p62 in the optic nerve was examined by immunoblot analysis 1 week after intravitreal injection.

Results : Intravitreal injection of ripasudil exerted significant axonal protection against TNF-induced optic nerve degeneration. Immunoblot analysis showed that increased p62 protein level induced by TNF was significantly inhibited by ripasudil. Treatment with ripasudil alone also decreased p62 protein levels in the optic nerve compared with the basal level.

Conclusions : ROCK inhibition may affect autophagy machinery in optic nerve. The modulation of p62 levels by ripasudil may be involved in part in its axonal protection.

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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