Axonal protection by short-term hyperglycemia with involvement of autophagy in TNF-induced optic nerve degeneration.
Axonal protection by short-term hyperglycemia with involvement of autophagy in TNF-induced optic nerve degeneration.
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DOI：
10.3389/fncel.2015.00425
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发表时间：
2015
影响因子：
5.3
通讯作者：
Takagi H
中科院分区：
文献类型：
--
作者：
Sase K;Kitaoka Y;Munemasa Y;Kojima K;Takagi H
以往的研究表明，短期高血糖对大鼠实验性高血压性青光眼模型的视神经轴突有保护作用。在这项研究中，我们研究了短期高血糖是否可以预防肿瘤坏死因子（TNF）诱导的大鼠视神经变性，并研究了自噬在轴突变化过程中的作用。在磷酸盐缓冲盐水（PBS）处理的大鼠眼中，在2周时，正常血糖（NG）和链脲佐菌素（STZ）诱导的高血糖（HG）组之间的轴突数量没有显著差异。玻璃体内注射TNF后2周，NG组轴突出现明显的退行性改变。然而，HG组对TNF诱导的视神经变性的轴突表现出显着的保护作用，与NG组相比。这种保护作用被自噬抑制剂3-甲基腺嘌呤（3-MA）显著抑制。免疫印迹分析显示，HG组视神经中LC 3-II水平高于NG组。在NG组中观察到TNF注射后视神经中p62蛋白水平增加，并且这种增加在HG组中被抑制。电镜下可见HG组视神经轴突内自噬体增多。免疫组化显示NG组和HG组LC 3与视网膜和视神经内的神经纤维共定位。短期高血糖保护轴突免受TNF诱导的视神经变性。这种轴突保护作用可能与自噬机制有关。
Previous reports showed that short-term hyperglycemia protects optic nerve axons in a rat experimental hypertensive glaucoma model. In this study, we investigated whether short-term hyperglycemia prevents tumor necrosis factor (TNF)-induced optic nerve degeneration in rats and examined the role of autophagy in this axon change process. In phosphate-buffered saline (PBS)-treated rat eyes, no significant difference in axon number between the normoglycemic (NG) and streptozotocin (STZ)-induced hyperglycemic (HG) groups was seen at 2 weeks. Substantial degenerative changes in the axons were noted 2 weeks after intravitreal injection of TNF in the NG group. However, the HG group showed significant protective effects on axons against TNF-induced optic nerve degeneration compared with the NG group. This protective effect was significantly inhibited by 3-methyladenine (3-MA), an autophagy inhibitor. Immunoblot analysis showed that the LC3-II level in the optic nerve was increased in the HG group compared with the NG group. Increased p62 protein levels in the optic nerve after TNF injection was observed in the NG group, and this increase was inhibited in the HG group. Electron microscopy showed that autophagosomes were increased in optic nerve axons in the HG group. Immunohistochemical study showed that LC3 was colocalized with nerve fibers in the retina and optic nerve in both the NG and HG groups. Short-term hyperglycemia protects axons against TNF-induced optic nerve degeneration. This axonal-protective effect may be associated with autophagy machinery.