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Kaori Kojima, Yasushi Kitaoka, Yasunari Munemasa, Satoki Ueno; Induction of autophagy prevents increase of p-PS1 in TNF-induced optic nerve axonal degeneration. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1419.
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We previously reported that an increase in phosphorylated presenilin 1 (p-PS1) in optic nerve may be associated with TNF-induced axonal degeneration. In this study, we investigated the involvement of autophagy in this condition.
Eight-week-old Wistar rats were received intravitreal injection of 10ng TNF alone or simultaneous injection of TNF and rapamycin into the right eyes. PBS was injected contralateral left eyes as control. Eyes were obtained 1 and 2 weeks after intravitreal injection. Levels of p-PS1 protein in optic nerve were determined by Western blot analysis. The effect of rapamycin on TNF-induced axonal degeneration was examined with optic nerve cross sections stained with 1% paraphenylene-diamine. The quantification was performed with Aphelion software.
Western blot analysis showed increases in p-PS1 protein levels in optic nerve after TNF injection compared with those after PBS injection and that these increases were significantly prevented by rapamycin treatment. Morphometric analysis showed that rapamycin ameliorated axon loss induced by TNF.
These results suggest that induction of autophagy may be protective against TNF-induced optic nerve degeneration with inhibition of p-PS1.
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