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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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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.
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.
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.
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.
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