Three-dimensional evaluation of retinal ganglion cell axon regeneration and pathfinding in whole mouse tissue after injury.
Three-dimensional evaluation of retinal ganglion cell axon regeneration and pathfinding in whole mouse tissue after injury.
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DOI：
10.1016/j.expneurol.2013.03.001
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发表时间：
2013-09
影响因子：
5.3
通讯作者：
Park, Kevin K.
中科院分区：
文献类型：
--
作者：
Luo, Xueting;Salgueiro, Yadira;Beckerman, Samuel R.;Lemmon, Vance P.;Tsoulfas, Pantelis;Park, Kevin K.
受损的视网膜神经节细胞（RGC）轴突不能自发再生，导致青光眼和创伤后视力丧失。最近的研究已经确定了几种诱导视神经长距离再生的策略。因此，现在一个紧迫的问题是再生的RGC轴突能否找到合适的靶点。评估RGC轴突再生的传统方法使用组织切片。然而，组织切片提供关于轴突轨迹和终止的零碎信息。为了明确评估再生RGC轴突，在这里，我们应用组织清除和光片荧光显微镜（LSFM）成像整个视神经和大脑没有物理切片。在具有PTEN/SOCS 3缺失的小鼠中，已知这种情况可以促进强大的再生，轴突生长遵循通过视神经的曲折路径，许多轴突逆转路线并向眼睛延伸。这种异常生长普遍存在于视神经的近端区域，其中存在强烈的星形胶质细胞活化。在PTEN/SOCS 3缺失小鼠和PTEN缺失/Zymosan/cAMP小鼠的视交叉中，许多轴突投射到对侧视神经或同侧视束。在双侧视神经挤压后，与单侧挤压相比，在视交叉处观察到类似的分叉轨迹。在中枢，轴突投射主要局限于下丘脑。总之，我们证明了LSFM的适用性，全面评估视神经再生，提供深入分析的轴突轨迹和寻路。我们的研究表明在视神经和大脑中存在显著的轴突误导，并强调了在成人视神经再生过程中研究轴突引导机制的必要性。
Injured retinal ganglion cell (RGCs) axons do not regenerate spontaneously, causing loss of vision in glaucoma and after trauma. Recent studies have identified several strategies that induce long distance regeneration in the optic nerve. Thus, a pressing question now is whether regenerating RGC axons can find their appropriate targets. Traditional methods of assessing RGC axon regeneration use histological sectioning. However, tissue sections provide fragmentary information about axonal trajectory and termination. To unequivocally evaluate regenerating RGC axons, here we apply tissue clearance and light sheet fluorescence microscopy (LSFM) to image whole optic nerve and brain without physical sectioning. In mice with PTEN/SOCS3 deletion, a condition known to promote robust regeneration, axon growth followed tortuous paths through the optic nerve, with many axons reversing course and extending toward the eye. Such aberrant growth was prevalent in the proximal region of the optic nerve where strong astroglial activation is present. In the optic chiasms of PTEN/SOCS3 deletion mice and PTEN deletion/Zymosan/cAMP mice, many axons project to the opposite optic nerve or to the ipsilateral optic tract. Following bilateral optic nerve crush, similar divergent trajectory is seen at the optic chiasm compared to unilateral crush. Centrally, axonal projection is limited predominantly to the hypothalamus. Together, we demonstrate the applicability of LSFM for comprehensive assessment of optic nerve regeneration, providing in-depth analysis of the axonal trajectory and pathfinding. Our study indicates significant axon misguidance in the optic nerve and brain, and underscores the need for investigation of axon guidance mechanisms during optic nerve regeneration in adults.
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影响因子：
33.6
作者：
Do MT;Yau KW
通讯作者：
Yau KW
影响因子：
16.2
作者：
Kuwajima T;Yoshida Y;Takegahara N;Petros TJ;Kumanogoh A;Jessell TM;Sakurai T;Mason C
通讯作者：
Mason C
影响因子：
5.3
作者：
Liu, X;Hawkes, E;Sretavan, DW
通讯作者：
Sretavan, DW
影响因子：
5.1
作者：
Leaver, S. G.;Cui, Q.;Harvey, A. R.
通讯作者：
Harvey, A. R.
影响因子：
2.5
作者：
BOHN, RC;STELZNER, DJ
通讯作者：
STELZNER, DJ