Tau Is Involved in Death of Retinal Ganglion Cells of Rats From Optic Nerve Crush
Tau Is Involved in Death of Retinal Ganglion Cells of Rats From Optic Nerve Crush
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DOI：
10.1167/iovs.19-26683
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发表时间：
2019-05-01
影响因子：
4.4
通讯作者：
Ikeda, Tsunehiko
中科院分区：
文献类型：
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作者：
Oku, Hidehiro;Kida, Teruyo;Ikeda, Tsunehiko
目的。确定牛头病变是否与自噬受损有关，并参与视神经挤压（ONC）大鼠视网膜神经节细胞（rgc）死亡。在ONC前48小时，将tau基因（si-Tau）的短干扰RNA （siRNA）或非靶向siRNA （si-NC）注射到玻璃体内。通过ONC后第7天和第14天tuj -1染色的RGCs数量来确定沉默tau基因对神经保护的影响。第7天采用免疫印迹和免疫组织化学方法检测磷酸化tau蛋白、P62蛋白和LC3B蛋白的表达变化。ONC后第7天，视网膜自噬受损，P62水平比假对照水平增加了3.1倍，LC3B2/LC3B1比值降低。视网膜中磷酸化tau蛋白（ser 396）增加2.1倍，si-Tau蛋白抑制其增加1.3倍（n = 3）。tau和P62的表达具有良好的共定位。在RGCs的胞体和视网膜神经纤维（rnf）中观察到这些表达，ONC后这些表达增加。si-Tau预处理对ONC后rgc的数量有显著的保护作用。si-NC组第14天RGCs密度为540 +/- 74.5个细胞/mm(2)， si-Tau组维持在1321 +/- 192个细胞/mm(2)（各n = 4）。沉默tau基因具有神经保护作用，tau病变可能与ONC后RGCs的死亡有关。受损的自噬可能与onc诱导的牛头病变有关。
PURPOSE. To determine whether tauopathies are associated with impaired autophagy and involved in the death of retinal ganglion cells (RGCs) of rats from an optic nerve crush (ONC).METHODS. Short interfering RNA (siRNA) of the tau gene (si-Tau) or nontargeting siRNA (si-NC) was injected intravitreally 48 hours prior to ONC. The effects of silencing the tau gene on neuroprotection were determined by the number of Tuj-1-stained RGCs on days 7 and 14 after the ONC. The changes in the expressions of phosphorylated tau, P62, and LC3B were determined by immunoblots and immunohistochemistry on day 7.RESULTS. Autophagy was impaired in the retina on day 7 after the ONC as the P62 level increased by 3.1-fold from the sham control level with a reduction in the ratio LC3B2/LC3B1. There was a 2.1-fold increase of phosphorylated tau (ser 396) in the retina, and si-Tau depressed the increase by 1.3-fold (n = 3 each). The expressions of tau and P62 were well colocalized. They were observed in the somas of RGCs and retinal nerve fibers (RNFs), and these expressions were increased after the ONC. Pretreatment by si-Tau showed significant protection in the number of RGCs after the ONC. Specifically, the density of RGCs was 540 +/- 74.5 cells/mm(2) on day 14 in the si-NC group, while the level was maintained at 1321 +/- 192 cells/mm(2) in the si-Tau group (n = 4 each).CONCLUSIONS. Silencing the tau gene is neuroprotective, and tauopathies may be involved in the death of RGCs after ONC. Impaired autophagy may be involved in ONC-induced tauopathies.