Dissociation of enhanced ornithine decarboxylase activity and optic nerve regeneration in goldfish

Abstract

The significance of a previously observed increase in retinal ornithine decarboxylase (ODC, EC 4.1.1.17) following optic nerve crush was investigated in goldfish using a specific irreversible inhibitor of ODC, [alpha]-difluoromethylornithine (DFMO). Retinal ODC activity and putrescine levels were reduced 80% and 40%, respectively, by intraperitoneal injection(s) of DFMO. In fish in which the right optic nerve was crushed and DFMO was injected at the time of crush, at 2 days and at 4 days later, retinal ODC levels were maximally decreased after the third injection and returned to normal levels by 14 days post-crush (PC).Retinal tubulin synthesis was examined at 10 days PC. No difference in the post-crush/normal ratio of tubulin synthesis was observed between saline-injected and DFMO-injected groups. Neuritic extension was also examined in retinal explant cultures from 11-day PC retina. The neuritic growth index of DFMO-treated retinas did not differ from that of control retinas. Behavioral studies revealed no difference in the rate of recovery of vision between the two groups. Similar results were obtained in experiments using fish maintained in a 0.1% DFMO solution.These results suggest that the increase in retinal ODC associated with nerve crush does not play a causal role in restoration of function.