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

Axonal protection by tacrolimus with inhibition of NFATc1 in TNF-induced optic nerve degeneration
Author Affiliations & Notes
  • Chihiro Tsukahara
    Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Japan
    Molecular Neuroscience, St. Marianna University Graduate School of Medicine, Kawasaki, Japan
  • 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
  • Hitoshi Takagi
    Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Japan
  • Footnotes
    Commercial Relationships   Chihiro Tsukahara, None; Yasushi Kitaoka, None; Kana Sase, None; Hitoshi Takagi, None
  • Footnotes
    Support  KAKENHI 15K10908
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 626. doi:
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    • Get Citation

      Chihiro Tsukahara, Yasushi Kitaoka, Kana Sase, Hitoshi Takagi;
      Axonal protection by tacrolimus with inhibition of NFATc1 in TNF-induced optic nerve degeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):626.

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

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Abstract

Purpose :
Tacrolimus, a calcineurin inhibitor, has been used for treatment of refractory allergic ocular diseases, although its role in optic nerve degeneration remains to be elucidated. In this study, we investigated whether tacrolimus modulates TNF-mediated axonal degeneration and it alters nuclear factor of activated T cells (NFATc) which is a downstream effector of calcineurin signaling.

Methods :
Experiments were carried out on Wistar rats that received 2 µl intravitreal injections of 10ng TNF, TNF+10-6 M tacrolimus, TNF+10-5 M tacrolimus, or TNF+10-4 M tacrolimus. PBS was administered into the contralateral eyes as a control. Levels of calcineurin Aα and NFATc1 protein in retina and optic nerve were examined by immunoblotting 3 days, 1 week, or 2 weeks after intravitreal injection. The effect of tacrolimus on axonal loss was evaluated by quantification of axon numbers 2 weeks after injection.

Results : Treatment of tacrolimus significantly ameliorated the TNF-mediated axonal loss (10-5 M: p = 0.0149 vs. TNF; 10-4 M: p = 0.0013 vs. TNF). No significant changes in calcineurin Aα protein level were observed in retina and optic nerve at any time points after TNF injection. However, a significant increase in NFATc1 protein level was observed in optic nerve 1 week after TNF injection. This increase was significantly prevented by tacrolimus.

Conclusions : NFATc1 may play a pivotal role in TNF-induced axonal degeneration. Tacrolimus exerts substantial axonal protection with an inhibitory effect on NFATc1.

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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