Systemic colchicine inhibits goldfish optic nerve regeneration

Abstract

Experiments were carried out to further investigate the regenerating goldfish optic nerve as a preparation for screening drugs or environmental toxins for adverse effects on neuronal circuit development. Regeneration was induced by unilateral retrobulbar optic nerve crush, and the opposite eye was kept intact. The time to recovery of vision was measured, as an index of regeneration and neurotoxicity, by an improved behavioral technique. The visual stimulus was changed to eliminate extraretinal photoresponding and to permit testing for vision with the right or left eye independently in a trial. Visual recovery occurred within 14 to 25 days. Colchicine, a potent inhibitor of microtubules and axonal transport, was administered semiweekly by ip injection, as in earlier experiments, to study the efficacy of the protocol. The drug resulted in an inhibition of regeneration at doses up to 0.2 [mu]g/g body wt which did not impair responding with the control eye. Administration of [beta]-lumicolchicine, a photoisomer of colchicine that is a weak inhibitor of microtubules or axonal transport, up to 2.0 [mu]g/g body wt, had no effect on regeneration or maintenance of visual responding. The results support the thesis that regenerating circuits are more sensitive indicators of neurotoxicity than are established circuits and confirm that the regenerating optic nerve can be used to screen molecules that may impair neuronal circuit development in vivo and to measure their relative potency.