Dezawa M, Adachi-Usami E
Department of Ophthalmology, Chiba University School of Medicine, Chiba City, Japan.
Prog Retin Eye Res. 2000 Mar;19(2):171-204. doi: 10.1016/s1350-9462(99)00010-5.
It is a well known fact that the injured PNS can successfully regenerate, on the other hand, the CNS such as retinal ganglion cell (RGC) axons of adult mammals is incapable of regeneration. After injury, RGC axons rapidly degenerate and most cell bodies go through the process of cell death, while glial cells at the site of injury undergo a series of responses which underlie the so-called glial scar formation. However, it has become apparent that RGCs do have an intrinsic capacity to regenerate which can be elicited by experimental replacement of the inhibitory glial environment with a permissive peripheral nerve milieu. Schwann cells are a major component of the PNS and play a role in regeneration, by producing various kinds of functional substances such as diffusible neurotrophic factors, extracellular matrix and cell adhesion molecules. RGC regeneration can be induced by cooperation of these substances. The contact of RGC axons to Schwann cells based upon the structural and molecular linkages seems to be indispensable for the stable and successful regeneration. In addition to cell adhesion molecules such as NCAM and L1, data from our laboratory show that Schwann cells utilize short focal tight junctions to provide morphological stabilization of the contact with the elongating axon, as well as a small scale of gap junctions to facilitate traffic of substances between them. Moreover, our results show that modifications of functional properties in neighboring glial cells of optic nerve are induced by transplantation of Schwann cells. Astrocytes usually considered to form a glial scar guide the regenerating axons in cooperation with Schwann cells. A decrease of the oligodendrocyte marker O4 and migration of ED-1 positive macrophages is observed within the optic nerve stump. Accordingly, RGC regeneration is not a simple phenomenon of axonal elongation on the Schwann cell membrane, but is based on direct and dynamic communication between the axon and the Schwann cell, and is also accompanied by changes and responses among the glial cell populations, which may be partly associated with the mechanisms of optic nerve regeneration.
众所周知，受损的周围神经系统（PNS）能够成功再生，而成年哺乳动物的中枢神经系统（CNS），如视网膜神经节细胞（RGC）轴突则无法再生。损伤后，RGC轴突迅速退化，大多数细胞体经历细胞死亡过程，而损伤部位的胶质细胞会发生一系列反应，这些反应构成了所谓的胶质瘢痕形成的基础。然而，很明显RGC确实具有内在的再生能力，通过用允许的周围神经环境实验性替代抑制性胶质环境可以引发这种能力。雪旺细胞是PNS的主要组成部分，通过产生各种功能性物质，如可扩散的神经营养因子、细胞外基质和细胞粘附分子，在再生中发挥作用。这些物质的协同作用可诱导RGC再生。基于结构和分子联系，RGC轴突与雪旺细胞的接触似乎是稳定和成功再生所必需的。除了神经细胞粘附分子（NCAM）和L1等细胞粘附分子外，我们实验室的数据表明，雪旺细胞利用短的紧密连接来为与伸长轴突的接触提供形态稳定性，以及利用小规模的缝隙连接来促进它们之间的物质运输。此外，我们的结果表明，雪旺细胞移植可诱导视神经邻近胶质细胞功能特性的改变。通常认为形成胶质瘢痕的星形胶质细胞与雪旺细胞协同引导再生轴突。在视神经残端观察到少突胶质细胞标志物O4减少和ED-1阳性巨噬细胞迁移。因此，RGC再生不是轴突在雪旺细胞膜上简单的伸长现象，而是基于轴突与雪旺细胞之间直接和动态的通讯，并且还伴随着胶质细胞群体之间的变化和反应，这可能部分与视神经再生的机制有关。
