Department of Molecular Neuroscience, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan.
Department of Ophthalmology, St. Marianna University School of Medicine, Kawasaki, Japan.
Jpn J Ophthalmol. 2020 May;64(3):298-303. doi: 10.1007/s10384-020-00731-6. Epub 2020 Mar 10.
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 SIRT1 activator SRT2104 exerts axonal protection in TNF-induced optic nerve degeneration. This effect may be associated with upregulated autophagic status in the optic nerve.
研究 SIRT1 激活剂 SRT2104 对 TNF 诱导的视神经变性的影响，并探讨其是否影响轴突变性诱导后的自噬状态。
实验。
成年雄性 Wistar 大鼠接受单独玻璃体内注射 TNF、同时注射 SRT2104 和 TNF、或单独注射 SRT2104。通过免疫印迹分析评估视神经中的自噬状态，以检查 p62 和 LC3-II 的表达。通过计数轴突数量来确定 SRT2104 对 TNF 诱导的轴突丢失的影响。
与 TNF 处理组相比，2 皮摩尔 SRT2104 处理组的玻璃体内注射显示出对 TNF 诱导的轴突丢失的适度保护趋势，但在定量分析中没有显著差异。然而，在 20 或 200 皮摩尔处理组中发现了显著的保护作用。与基础水平相比，单独注射 SRT2104 显著降低了 p62 水平并增加了 LC3-II 水平。同样，与 TNF 处理组相比，同时注射 SRT2104 和 TNF 也显著降低了 p62 水平并增加了 LC3-II 水平。在 SRT2104 处理后观察到视神经中 SIRT1 表达的上调。
SIRT1 激活剂 SRT2104 对 TNF 诱导的视神经变性具有轴突保护作用。这种作用可能与视神经中自噬状态的上调有关。
