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