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Yasushi Kitaoka, Kaori Kojima, Yasunari Munemasa, Hitoshi Takagi; Induction of autophagy protects axons against TNF-induced optic nerve degeneration with possible involvement of p62 inhibition. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6233.
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To examine the role of p62 and autophagy in TNF-induced optic nerve degeneration.
Eight-week-old male Wistar rats were received intravitreal injection of 10 ng TNF alone or simultaneous injection of TNF and p62 siRNA (50 pmol). Intravitreal injection of rapamycin (2 μl; 1 mM) was also performed. The expression of p62 in optic nerve was examined by immunoblotting. The effects of p62 siRNA or rapamycin on axon were evaluated by axon number counting 2 weeks after intravitreal injection.
Immunoblotting showed that there was an increase in p62 protein level in optic nerve after TNF injection compared to the PBS injection and this increase was significantly inhibited by p62 siRNA. Rapamycin also significantly inhibited upregulation of p62 in optic nerve. Morphometric analysis showed that p62 siRNA significantly ameliorated axon loss induced by TNF. Rapamycin which is an autophagy inducer also significantly ameliorated axon loss induced by TNF.
Inhibition of p62 may have potential for axonal protection in TNF-induced optic nerve degeneration.
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