Local application of calcium-modulating agents to a crushed goldfish optic nerve modifies visual recovery

The effects of various Ca2+-modulating agents on regeneration in the optic nerve of goldfish were determined by assaying recovery of visual function. One to three daily applications of the agents were made at the site of an optic nerve crush beginning within 3 days after the lesion. Application of calcium ionophore A-23187 significantly shortened the time required for reappearance of the startle reaction to a bright light. Some shortening of recovery time was also observed with application of high-Ca2+ Ringer's solution. A significant effect was obtained with 1% and 6% dimethylsulfoxide (DMSO). When A-23187 was combined with DMSO, a further enhancement was seen if the original DMSO effect had been weak, whereas a strong DMSO effect was reduced in the presence of A-23187. The effect of DMSO alone or DMSO in combination with A-23187 was blocked by the calcium-chelating agent EGTA. These results indicated that increased entry of Ca2+ into the regenerating axons or supporting cells may be responsible for the enhanced rate of recovery. There was no histologic evidence that the faster recovery was due to accelerated axon outgrowth, but the packing density of the regenerating axons was increased. We postulate that the recovery-enhancing agents may act by promoting axonal interactions leading to the reestablishment of the correct retinal projection, or by facilitating the function of the regenerating synaptic terminals.