REGENERATION IN THE OPTIC-NERVE OF ADULT-RATS - INFLUENCES OF CULTURED ASTROCYTES AND OPTIC-NERVE GRAFTS OF DIFFERENT ONTOGENIC STAGES

We have studied the effects of transplanted optic nerves of different ontogenetic stages (E19 to adult), and cultured astrocytes from P2 cer ebral cortex on the regeneration of axons in the optic nerve of adult rats. Regeneration was visualized by anterograde tracing with rhodamin e-iso-thiocyanate. Grafts were identified with Nuclear Yellow. Astrogl ia within both the cut optic nerve and the transplants were detected b y anti-glial fibrillary acidic protein staining. In control animals (c ut optic nerve, 2-3 mm behind the optic disc), only a few neurites wer e found 15 days after the operation which grew randomly for short dist ances into the surrounding meningeal sheaths. Perinatal (E19 to P2) op tic nerves induced a massive outgrowth of RITC-filled axons from the h ost optic nerve. The regenerating fibres grew for up to 3 mm towards t he graft, ahead of glial fibrillary acidic protein-positive astroglia emanating from the host optic nerve that seemed to follow them. Althou gh the regenerating fibres reached the grafts, they did not penetrate them. Optic nerve grafts of increasing age elicited smaller growth res ponses; e.g. grafts from P8 promoted only a very limited (several 100 mu m) growth response, grafts from P12 and later induced outgrowth com parable with that of control animals. Grafted astrocytes from P2 donor s that had previously been grown in culture, were also capable of prom oting outgrowth of rhodamine-iso-thiocyanate-filled axons from the hos t optic nerve. These findings suggest that only astrocytes at an immat ure stage of differentiation are capable of inducing axon growth from the adult optic nerve. Furthermore, the absence of an obvious cellular bridge between host and graft suggests that the graft effect is proba bly mediated by the release of astrolglia-derived diffusible neurite g rowth promoting factors.