Mar 12, 2020

Axonal protection by a small molecule SIRT1 activator, SRT2104, with alteration of autophagy in TNF-induced optic nerve degeneration

Japanese Journal of Ophthalmology
Yasushi KitaokaHitoshi Takagi

Abstract

To examine the effects of SRT2104, an SIRT1 activator, in optic nerve degeneration induced by TNF and to investigate whether it affects the autophagic status after induction of axonal degeneration. Experimental. Adult male Wistar rats received intravitreal injection of TNF alone, concomitant injection of SRT2104 and TNF, or injection of SRT2104 alone. The autophagic status in the optic nerve was evaluated to examine p62 and LC3-II expression by immunoblot analysis. The effect of SRT2104 on TNF-induced axon loss was determined by counting the number of axons. Intravitreal injection of SRT2104 showed a modest protective tendency in the 2-pmol-treated groups against TNF-induced axon loss, although the tendency was not significant on quantitative analysis. However, significant protective effects were found in the 20- or 200-pmol-treated groups. Injection of SRT2104 alone significantly decreased the p62 levels and increased the LC3-II levels as compared with the basal levels. Similarly, concomitant injection of SRT2104 and TNF significantly decreased the p62 levels and increased the LC3-II levels as compared with the TNF-treated group. Upregulation of SIRT1 expression was observed in the optic nerve after SRT2104 treatment. The SIRT...Continue Reading

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Mentioned in this Paper

Tumor Necrosis Factor-alpha
Autophagosome
Exertion
Autophagy
SIRT1
SIRT1 protein, human
Up-Regulation (Physiology)
SIRT1 gene
Optic Nerve
TNF gene

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