Ornithine decarboxylase activity in retinal explants of goldfish undergoing optic nerve regeneration

Retinal explants cultured in the presence of fetal calf serum (FCS) exhibit an increase in the activity of ornithine decarboxylase which is maximal several hours after explantation. The measured activity of this enzyme is higher in explants of retinas whose optic nerve had been crushed several days previously (post-crush, PC) than in control (normal, N) retinas. The addition of rabbit antibodies against nerve growth factor (NGF) to the incubation medium does not block this stimulatory effect of FCS, a result suggesting that factors other than NGF present in FCS are responsible for the observed stimulation. An inhibitor of ODC synthesis, diaminopropane (DAP), and an irreversible inhibitor of ODC activity, alpha-DL-difluoromethylornithine (alpha-DFMO), each suppressed the FCS-stimulated ODC activity when added to the culture medium. Since FCS addition also promotes neuritic outgrowth from PC goldfish retinal explants, we explored the possible relationship of the stimulated ODC activity and the ability of explants to extend neurites. Concentrations of DAP or alpha-DFMO that block ODC activity also suppress neuritic outgrowth. Possible non-specific actions of the drugs unrelated to the block of ODC are examined. While the increases in OCD activity seen in PC and N goldfish retinas explanted into FCS-containing medium may be a requisite, they cannot be sufficient to support neuritic outgrowth. Intrinsic changes in the retinal explant secondary to crush of its optic nerve as well as factor(s) present in FCS that may be unrelated to the stimulation of ODC activity also appear necessary for neuritic outgrowth.