Will central nervous systems in the adult mammal regenerate after bypassing a lesion? A study in the mouse and chick visual systems

Abstract

We determined whether or not optic axons in the adult mammalian retina would regenerate well if allowed to bypass a lesion scar. In one series we produced microlesions with fine needles in the ganglion cell fiber layer of adult mouse retinas and later examined the retinas as silver-stained flat mounts to observe the behavior of optic axons that bypassed the lesion. Such axons continued to grow abortively, i.e., grew randomly and for only short distances, whether growing within a sector of Wallerian (anterograde) degeneration or in the neighboring zone of intact optic axon bundles. In a second series we produced optic nerve crushes in adult mice and observed the behavior of optic axons growing retrograde into the retina. These fibers similarly grew abortively whether in a zone of intact fiber bundles or when a retinal lesion was produced with the crush, in the sector of Wallerian degeneration. Retinal lesions in newly hatched chicks produced a comparable picture of abortive (short-distance) growth, but the optic and centrifugal fibers had a greater tendency to remain oriented within the ganglion cell fiber layer than did mouse axons. This improved orientation may be the consequence of the greater number of optic fibers in the chick retina and hence the greater opportunity for nonspecific contact guidance. The results indicate that blockage (by a lesion scar or myelin debris) and hypoxia are not the key causes of regenerative failure, as regeneration failed even when those factors were minimal.