3D Visualization of Individual Regenerating Retinal Ganglion Cell Axons Reveals Surprisingly Complex Growth Paths.
3D Visualization of Individual Regenerating Retinal Ganglion Cell Axons Reveals Surprisingly Complex Growth Paths.
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3D视网膜神经节细胞轴突的3D可视化揭示了令人惊讶的复杂生长路径。
DOI：
10.1523/eneuro.0093-17.2017
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发表时间：
2017-07
期刊：
影响因子：
3.4
通讯作者：
Tsoulfas P
中科院分区：
文献类型：
--
作者：
Bray ER;Noga M;Thakor K;Wang Y;Lemmon VP;Park KK;Tsoulfas P
视网膜神经节细胞(RGC)是视网膜的唯一输出细胞，是将轴突投射到大脑中视觉目标的异质性神经元群体。像大多数中枢神经系统神经元一样，视网膜节细胞被认为不具备长距离轴突再生的能力。利用转基因小鼠体内溶剂清除器官的免疫标记3D成像(IDISCO)，我们跟踪了单个RGC轴突的整个路径，并表明成年RGC即使在没有任何治疗的情况下也具有高度的自发远距离再生能力。我们的结果表明，Thy1-H-YFP小鼠稀疏地标记RGC，主要由具有再生能力的α类型的RGC(αRGC)组成。视神经挤压后，许多YFP标记的RGC轴突延伸到损伤部位近端相当远的距离，只有少数穿过病变。在接受睫状神经营养因子(CNTF)治疗的情况下，病变部位近端曲折的轴突生长更加明显。我们进一步证明，尽管移动超过5毫米(即相当于小鼠视神经长度的距离)，许多这些迂回的轴突仅限于损伤区域，无法到达大脑。我们的结果重新评估了RGC天生不能重新延伸长轴突的观点，并将重点从促进轴突延长转移到了解阻止轴突通过病变和受损神经直接生长的因素。
Retinal ganglion cells (RGCs), the sole output cells of the retina, are a heterogeneous population of neurons that project axons to visual targets in the brain. Like most CNS neurons, RGCs are considered incapable of mounting long distance axon regeneration. Using immunolabeling-enabled 3D imaging of solvent-cleared organs (iDISCO) in transgenic mice, we tracked the entire paths of individual RGC axons and show that adult RGCs are highly capable of spontaneous long-distance regeneration, even without any treatment. Our results show that the Thy1-H-YFP mouse sparsely labels RGCs, consisting predominantly of regeneration-competent α-type RGCs (αRGCs). Following optic nerve crush, many of the YFP-labeled RGC axons extend considerable distances proximal to the injury site with only a few penetrating through the lesion. This tortuous axon growth proximal to the lesion site is even more striking with intravitreal ciliary neurotrophic factor (CNTF) treatment. We further demonstrate that despite traveling more than 5 mm (i.e., a distance equal to the length of mouse optic nerve), many of these circuitous axons are confined to the injury area and fail to reach the brain. Our results re-evaluate the view that RGCs are naturally incapable of re-extending long axons, and shift the focus from promoting axon elongation, to understanding factors that prevent direct growth of axons through the lesion and the injured nerve.