April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Phosphorylation of PS1 And Up-regulation of APP In TNF-induced Optic Nerve Degeneration
Author Affiliations & Notes
  • Kaori Kojima
    Ophthalmology, St Marianna Univ School of Med, Kawasaki, Japan
  • Yasushi Kitaoka
    Ophthalmology, St Marianna Univ School of Med, Kawasaki, Japan
  • Yasunari Munemasa
    Ophthalmology, St Marianna Univ School of Med, Kawasaki, Japan
  • Satoki Ueno
    Ophthalmology, St Marianna Univ School of Med, Kawasaki, Japan
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 4681. doi:
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    • Get Citation

      Kaori Kojima, Yasushi Kitaoka, Yasunari Munemasa, Satoki Ueno; Phosphorylation of PS1 And Up-regulation of APP In TNF-induced Optic Nerve Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4681.

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

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Abstract

Purpose: : Presenilins (PS) are important components of the γ-secretase complex that mediates cleavage of type I membrane proteins including the β-amyloid precursor protein (APP) to generate the amyloid β-peptide. The purpose of this study is to investigate the involvement of PS-1 and APP in TNF-induced optic nerve degeneration.

Methods: : Eight-week-old Wister rats were received intravitreal injection of 10ng TNF or PBS. Eyes were obtained animals 1 or 2 weeks after intravitreal injection. The protein levels of p-PS1, PS1, PS2, and APP in the optic nerve were examined by Western blot analysis. The localizations of p-PS1 and APP in the retina and optic nerve were detected by immunohistochemistry (IHC). The axonal degeneration was confirmed in cross-sections of optic nerve by light microscopy.

Results: : Western blot analysis showed increases in level of p-PS1, PS1 and APP proteins in the optic nerve 1week after TNF injection, compared with those after PBS injection. IHC confirmed increases in p-PS1 and APP immunoreactivities in the optic nerve 1week after TNF injection. Double-labeling analysis showed that the localization of p-PS1 was predominantly observed in vimentin-positive glial cells around optic nerve lamina portion after TNF injection. Immunoreactivities of APP were also detected in vimentin-positive glial cells after TNF injection.

Conclusions: : These results suggest that PS1 phosphorylation and upregulation of APP may play pivotal roles in optic nerve degeneration with involvement of glial activation after TNF intravitreal injection.

Keywords: optic nerve • glia • neuro-ophthalmology: optic nerve 
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