Axonal interactions with connective tissue and glial substrata during optic nerve regeneration in Xenopus larvae and adults.

Axonal elongation through connective tissue and glial environments was compared following resection of the optic nerves in Xenopus tadpoles and frogs. During initial stages of fiber outgrowth, axons encountered connective-tissue matrices of varying degrees of complexity in the ablation gaps. Many of the neuritic sprouts were randomly directed after leaving the retinal stump, and a neuroma-like swelling ultimately formed at the cut edge. Although a large number of axons managed to traverse the lesion and associate with the cranial stump, many other fibers were less appropriately directed, especially in the frog where a greater infiltration of dense collagen occurred between the separated segments of the optic nerve. Axons often deviated from their cranially oriented pattern of outgrowth after entering the lesion and invaded surrounding extraocular muscles; others advanced along neighboring blood vessels and cranial nerve branches. In more extreme circumstances, fibers were completely misdirected at the cut end of the retinal stump and ultimately extended adjacent to the retinal segment back toward the eye. A more organized pattern of axonal elongation was observed in the presence of the glial substratum of the central stump, and growth cones appeared to associate preferentially with astrocyte endfeet in both tadpoles and frogs. These observations show that axons in the regenerating optic nerve of the amphibian can interact with a variety of cells and tissues and that the general direction of their outgrowth, at least in more peripheral regions of the visual pathway, appears to be dependent upon the orientation and, possibly, molecular properties of the terrain which they contact. In general, the basic environmental factors which either foster or impede axonal elongation in this regenerating system appear analogous to those influencing fiber outgrowth during regeneration in the peripheral nervous system of various species.