Role of Schwann cells in retinal ganglion cell axon regeneration

It is a well known fact that the injured PNS can successfully regenerate, o n the other hand, the CNS such as retinal ganglion cell (RGC) axons of adul t mammals is incapable of regeneration. After injury, RGC axons rapidly deg enerate and most cell bodies go through the process of fell death, while di al cells at the site of injury undergo a series of responses which underlie the so-called dial scar formation. However, it has become apparent that RG Cs do have an intrinsic capacity to regenerate which can be elicited by exp erimental replacement of the inhibitory dial 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 subs tances such as diffusible neurotrophic factors, extracellular matrix and ce ll adhesion molecules. RGC regeneration can be induced by cooperation of th ese substance;. The contact of RGC axons to Schwann cells based upon the st ructural and molecular linkages seems to be indispensable for the stable an d successful regeneration. In addition to cell adhesion molecules such as N CAM 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 fac ilitate traffic of substances between them. Moreover, our results show that modifications of functional properties in neighboring dial cells of optic nerve are induced by transplantation of Schwann cells. Astrocytes usually c onsidered to form a dial scar guide the regenerating axons in cooperation w ith Schwann cells. A decrease of the oligodendrocyte marker O4 and migratio n of ED-I positive macrophages is observed within the optic nerve stump. Ac cordingly, RGC regeneration is not a simple phenomenon of axonal elongation on the Schwann cell membrane. but is based on direct and dynamic communica tion between the axon and the Schwann cell, and is also accompanied by chan ges and responses among the glial cell populations, which may be partly ass ociated with the mechanisms of optic nerve regeneration. (C) 2000 Elsevier Science Ltd. All rights reserved.