Growth-associated protein43 (GAP43) is a biochemical marker for the whole period of fish optic nerve regeneration.

In adult visual system, goldfish can regrow their axons and fully restore their visual function even after optic nerve transection. The optic nerve regeneration process in goldfish is very long and it takes about a half year to fully recover visual function via synaptic refinement. Therefore, we investigated time course of growth-associated protein 43 (GAP43) expression in the goldfish retina for over 6 months after axotomy. In the control retina, very weak immunoreactivity could be seen in the retinal ganglion cells (RGCs). The immunoreactivity of GAP43 started to increase in the RGCs at 5 days, peaked at 7-20 days and then gradually decreased at 30-40 days after axotomy. The weak but significant immunoreactivity of GAP43 in the RGCs continued during 50-90 days and slowly returned to the control level by 180 days after lesion. The levels of GAP43 mRNA showed a biphasic pattern; a short-peak increase (9-folds) at 1-3 weeks and a long plateau increase (5-folds) at 50-120 days after axotomy. Thereafter, the levels declined to the control value by 180 days after axotomy. The changes of chasing behavior of pair of goldfish with bilaterally axotomized optic nerve also showed a slow biphasic recovery pattern in time course. Although further experiment is needed to elucidate the role of GAP43 in the regrowing axon terminals, the GAP43 is a good biochemical marker for monitoring the whole period of optic nerve regeneration in fish.

Changes of phospho-growth-associated protein 43 (phospho-GAP43) in the zebrafish retina after optic nerve injury: a long-term observation.

The major model animal of optic nerve regeneration in fish is goldfish. A closely related zebrafish is the most popular model system for genetic and developmental studies of vertebrate central nervous system. A few challenging works of optic nerve regeneration have been done with zebrafish. However, knowledge concerning the long term of optic nerve regeneration apparently lacks in zebrafish. In the present study, therefore, we followed changes of zebrafish behavior and phosphorylated form of growth-associated protein 43 (phospho-GAP43) expression in the zebrafish retina over 100 days after optic nerve transection. Optomotor response was fast recovered by 20-25 days after axotomy whereas chasing behavior (a schooling behavior) was slowly recovered by 80-100 days after axotomy. The temporal pattern of phospho-GAP43 expression showed a biphasic increase, a short-peak (12 folds) at 1-2 weeks and a long-plateau (4 folds) at 1-2 months after axotomy. The recovery of optomotor response well correlated with projection of growing axons to the tectum, whereas the recovery of chasing behavior well correlated with synaptic refinement of retinotectal topography. The present data strongly suggest that phospho-GAP43 plays an active role in both the early and late stages of optic nerve regeneration in fish.