Restoration of Visual Function by Enhancing Conduction in Regenerated Axons.
Restoration of Visual Function by Enhancing Conduction in Regenerated Axons.
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DOI：
10.1016/j.cell.2015.11.036
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发表时间：
2016-01-14
期刊：
影响因子：
64.5
通讯作者：
He Z
中科院分区：
文献类型：
--
作者：
Bei F;Lee HHC;Liu X;Gunner G;Jin H;Ma L;Wang C;Hou L;Hensch TK;Frank E;Sanes JR;Chen C;Fagiolini M;He Z
虽然许多修复策略已经被证明可以促进哺乳动物中枢神经系统神经元损伤后的轴突生长，但再生的轴突是否建立功能性突触和支持行为仍不清楚。在幼年和成年小鼠中，我们发现PTEN和SOCS3的共同缺失，或骨桥蛋白(OPN)/胰岛素样生长因子1(IGF1)/睫状神经营养因子(CNTF)的共同过表达，都能诱导视网膜轴突的再生和上丘(SC)功能性突触的形成，但视觉功能没有明显恢复。进一步的分析表明，由于缺乏髓鞘，再生的轴突无法将动作电位从眼睛传导到SC。与这一想法一致的是，使用电压门控钾通道阻滞剂可以恢复传导并提高视力。因此，加强再生和传导能有效地改善视神经损伤后的功能。
Although a number of repair strategies have been shown to promote axon outgrowth following neuronal injury in the mammalian central nervous system, it remains unclear whether regenerated axons establish functional synapses and support behavior. Here, in both juvenile and adult mice, we show that either PTEN and SOCS3 co-deletion, or co-overexpression of osteopontin (OPN)/insulin-like growth factor 1 (IGF1)/ciliary neurotrophic factor (CNTF), induces regrowth of retinal axons and formation of functional synapses in the superior colliculus (SC), but not significant recovery of visual function. Further analyses suggest that regenerated axons fail to conduct action potentials from the eye to the SC due to lack of myelination. Consistent with this idea, administration of voltage-gated potassium channel blockers restores conduction and results in increased visual acuity. Thus, enhancing both regeneration and conduction effectively improves function after optic nerve injury.