UP-REGULATION OF FAST-AXONALLY TRANSPORTED PROTEINS IN RETINAL GANGLION-CELLS OF ADULT RATS WITH OPTIC-PERONEAL NERVE GRAFTS

Metabolic labeling and quantitative 2D gel fluorography were used to a ssess changes in the synthesis and transport of five fast-axonally tra nsported and developmentally regulated proteins (GAP-43, SNAP-25, and proteins of 18, 22, and 23/24 kDa) after grafting of a peroneal nerve segment onto a transected optic nerve in adult rats. After optic nerve transection alone, only GAP-43 was up-regulated significantly compare d to normal adult controls. The other proteins showed little change or were down-regulated following axotomy. By 4 weeks following optic ner ve transection and peroneal nerve grafting, however, GAP-43, proteins 22 and 23/24 kDa showed a sustained up-regulation in synthesis and tra nsport compared to normal controls; SNAP-25 and protein 18 kDa showed levels of expression similar to or slightly greater than normal contro ls. Increased expression of GAP-43 in retinal ganglion cells was also examined with immunocytochemistry. While a transient up-regulation of GAP-43 in retinal ganglion cells was observed following optic nerve tr ansection, a sustained increase in GAP-43 immunoreactivity was present only in animals with nerve grafts. Backfilling of retinal ganglion ce lls from the grafts with horseradish peroxidase combined with GAP-43 i mmunocytochemistry revealed that all retinal ganglion cells with axons growing into the grafts were positive for GAP-43, but not all retinal ganglion cells showing GAP-43 immunoreactivity were extending axons i nto the grafts. We conclude that the presence of a nerve graft sustain s the up-regulation of a number of proteins including GAP-43, and that this up-regulation is correlated with an increased potential for nerv e growth, but other as yet unknown factors or conditions appear to pla y a role in determining if this growth potential will be realized. (C) 1998 Elsevier Science B.V.