Spermidine promotes retinal ganglion cell survival and optic nerve regeneration in adult mice following optic nerve injury.
Spermidine promotes retinal ganglion cell survival and optic nerve regeneration in adult mice following optic nerve injury.
复制标题
亚精胺促进视神经损伤后成年小鼠视网膜神经节细胞存活和视神经再生。
DOI：
10.1038/cddis.2015.93
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发表时间：
2015-04-16
影响因子：
9
通讯作者：
Harada T
中科院分区：
文献类型：
--
作者：
Noro T;Namekata K;Kimura A;Guo X;Azuchi Y;Harada C;Nakano T;Tsuneoka H;Harada T
亚精胺作为一种内源性自由基清除剂，抑制活性氧的作用。在这项研究中，我们研究了亚精胺对视神经损伤（ONI）小鼠模型视网膜神经节细胞（RGC）死亡的影响。每日摄入亚精胺可减少ONI后RGC死亡，连续体内视网膜成像显示亚精胺可有效预防视网膜变性。凋亡信号调节激酶1 （Apoptosis signal- regulatory kinase-1, ASK1）是一种进化保守的丝裂原活化蛋白激酶激酶，在oni诱导的RGC凋亡中起重要作用。我们证明亚精胺抑制oni诱导的ASK1-p38丝裂原激活蛋白激酶途径的激活。此外，亚精胺处理减少了对小胶质细胞募集重要的趋化因子的产生，因此，视网膜小胶质细胞的积累减少。此外，oni诱导的诱导型一氧化氮合酶在视网膜中的表达被亚精胺抑制，尤其是在小胶质细胞中。此外，每日摄入亚精胺可促进体内视神经再生。我们的研究结果表明，亚精胺刺激神经保护和神经再生，可能对治疗包括青光眼在内的各种神经退行性疾病有用。
Spermidine acts as an endogenous free radical scavenger and inhibits the action of reactive oxygen species. In this study, we examined the effects of spermidine on retinal ganglion cell (RGC) death in a mouse model of optic nerve injury (ONI). Daily ingestion of spermidine reduced RGC death following ONI and sequential in vivo retinal imaging revealed that spermidine effectively prevented retinal degeneration. Apoptosis signal-regulating kinase-1 (ASK1) is an evolutionarily conserved mitogen-activated protein kinase kinase kinase and has an important role in ONI-induced RGC apoptosis. We demonstrated that spermidine suppresses ONI-induced activation of the ASK1-p38 mitogen-activated protein kinase pathway. Moreover, production of chemokines important for microglia recruitment was decreased with spermidine treatment and, consequently, accumulation of retinal microglia is reduced. In addition, the ONI-induced expression of inducible nitric oxide synthase in the retina was inhibited with spermidine treatment, particularly in microglia. Furthermore, daily spermidine intake enhanced optic nerve regeneration in vivo. Our findings indicate that spermidine stimulates neuroprotection as well as neuroregeneration, and may be useful for treatment of various neurodegenerative diseases including glaucoma.