Symonds A C E, King C E, Bartlett C A, Sauvé Y, Lund R D, Beazley L D, Dunlop S A, Rodger J
School of Animal Biology M092, The University of Western Australia, 35 Stirling Highway, Crawley, Perth 6009, Western Australia.
Eur J Neurosci. 2007 Feb;25(3):744-52. doi: 10.1111/j.1460-9568.2007.05321.x.
During development, gradients of EphA receptors (nasal(low)-temporal(high)) and their ligands ephrin-As (rostral(low)-caudal(high)) are involved in establishing topography between retinal ganglion cells (RGCs) and the superior colliculus (SC). EphA5-expressing RGC axons are repulsed by ephrin-A2-expressing SC neurones. In adult rats RGCs maintain graded EphA5 expression but ephrin-A2 expression is down-regulated in the SC to a weak gradient. At 1 month after optic nerve transection, EphA5 expression is reduced in the few remaining RGCs and is no longer graded; by contrast, SC ephrin-A2 is up-regulated to a rostral(low)-caudal(high) gradient. Here we examined expression in adult rat 1 month after bridging the retina and SC with a peripheral nerve graft, a procedure that enhances RGC survival and permits RGC axon regeneration. Double labelling with cell markers revealed preservation of a nasal(low)-temporal(high) EphA5 gradient in RGCs and establishment of a rostral(low)-caudal(high) ephrin-A2 gradient within neurones of the SC. The results suggest a potential for guidance cues to restore the topography of RGC axons in the SC. However, high ephrin-A2 levels were also found in astrocytes surrounding the peripheral nerve graft insertion site. The repulsive ephrin-A2 environment offers at least a partial explanation for the observation that only a limited number of RGC axons can exit the graft to enter target central nervous system tissue.
在发育过程中，EphA受体（鼻侧（低）-颞侧（高））及其配体ephrin-A（嘴侧（低）-尾侧（高））的梯度参与建立视网膜神经节细胞（RGC）与上丘（SC）之间的拓扑结构。表达EphA5的RGC轴突受到表达ephrin-A2的SC神经元的排斥。在成年大鼠中，RGC维持EphA5的梯度表达，但SC中ephrin-A2的表达下调至弱梯度。视神经横断后1个月，少数残留的RGC中EphA5表达降低且不再呈梯度分布；相反，SC中的ephrin-A2上调至嘴侧（低）-尾侧（高）梯度。在此，我们检测了成年大鼠在通过外周神经移植连接视网膜和SC 1个月后的表达情况，该操作可提高RGC的存活率并允许RGC轴突再生。用细胞标记物进行双重标记显示，RGC中鼻侧（低）-颞侧（高）的EphA5梯度得以保留，且SC神经元内建立了嘴侧（低）-尾侧（高）的ephrin-A2梯度。结果表明，引导信号有可能恢复SC中RGC轴突的拓扑结构。然而，在外周神经移植插入部位周围的星形胶质细胞中也发现了高浓度的ephrin-A2。这种具有排斥性的ephrin-A2环境至少部分解释了为何只有有限数量的RGC轴突能够离开移植体进入目标中枢神经系统组织这一现象。
