Paşcalău Raluca, Badea Tudor Constantin
Research and Development Institute, Transilvania University of Braşov, Braşov, Romania.
Ophthalmology Clinic, Cluj County Emergency Hospital, Cluj-Napoca, Romania.
Front Ophthalmol (Lausanne). 2023 May 17;3:1180142. doi: 10.3389/fopht.2023.1180142. eCollection 2023.
Sending an axon out of the eye and into the target brain nuclei is the defining feature of retinal ganglion cells (RGCs). The literature on RGC axon pathfinding is vast, but it focuses mostly on decision making events such as midline crossing at the optic chiasm or retinotopic mapping at the target nuclei. In comparison, the exit of RGC axons out of the eye is much less explored. The first checkpoint on the RGC axons' path is the optic cup - optic stalk junction (OC-OS). OC-OS development and the exit of the RGC pioneer axons out of the eye are coordinated spatially and temporally. By the time the optic nerve head domain is specified, the optic fissure margins are in contact and the fusion process is ongoing, the first RGCs are born in its proximity and send pioneer axons in the optic stalk. RGC differentiation continues in centrifugal waves. Later born RGC axons fasciculate with the more mature axons. Growth cones at the end of the axons respond to guidance cues to adopt a centripetal direction, maintain nerve fiber layer restriction and to leave the optic cup. Although there is extensive information on OC-OS development, we still have important unanswered questions regarding its contribution to the exit of the RGC axons out of the eye. We are still to distinguish the morphogens of the OC-OS from the axon guidance molecules which are expressed in the same place at the same time. The early RGC transcription programs responsible for axon emergence and pathfinding are also unknown. This review summarizes the molecular mechanisms for early RGC axon guidance by contextualizing mouse knock-out studies on OC-OS development with the recent transcriptomic studies on developing RGCs in an attempt to contribute to the understanding of human optic nerve developmental anomalies. The published data summarized here suggests that the developing optic nerve head provides a physical channel (the closing optic fissure) as well as molecular guidance cues for the pioneer RGC axons to exit the eye.
将轴突送出眼睛并进入目标脑核是视网膜神经节细胞（RGCs）的决定性特征。关于RGC轴突寻路的文献浩如烟海，但大多集中在决策事件上，比如在视交叉处的中线交叉或在目标核处的视网膜拓扑映射。相比之下，RGC轴突穿出眼睛的过程则较少被探索。RGC轴突路径上的第一个检查点是视杯 - 视柄交界处（OC - OS）。OC - OS的发育以及RGC先驱轴突穿出眼睛的过程在空间和时间上是协调的。当视神经乳头区域确定时，视裂边缘相互接触且融合过程正在进行，第一批RGC在其附近产生，并将先驱轴突发送到视柄中。RGC的分化以离心波的形式持续进行。后来产生的RGC轴突与更成熟的轴突成束。轴突末端的生长锥对导向线索做出反应，以采取向心方向，维持神经纤维层的限制并离开视杯。尽管关于OC - OS发育有大量信息，但关于其对RGC轴突穿出眼睛的贡献，我们仍有一些重要的未解决问题。我们仍需区分OC - OS的形态发生素与同时在同一位置表达的轴突导向分子。负责轴突出现和寻路的早期RGC转录程序也尚不清楚。本综述通过将关于OC - OS发育的小鼠基因敲除研究与最近关于发育中的RGC的转录组学研究相结合，总结了早期RGC轴突导向的分子机制，试图有助于理解人类视神经发育异常。此处总结的已发表数据表明，发育中的视神经乳头为先驱RGC轴突穿出眼睛提供了一个物理通道（闭合的视裂）以及分子导向线索。
