Intraocular tetrodotoxin in goldfish hinders optic nerve regeneration.
Repeated intraocular injection of tetrodotoxin (TTX) was used to produce a maintained block of neural activity in goldfish optic axons which were regenerating following a crush of the optic nerve. The recovery of visual function was delayed in the TTX-treated fish, as demonstrated by delays in the return of the startle reaction to sudden illumination, the dorsal light reflex and food pellet localization. A single injection of TTX at the time of optic nerve crush delayed recovery of the startle reaction but not of food localization. There was no loss of ganglion cells in the TTX-treated animals, but the number of regenerated axons detectable by light microscopy was reduced. Also, axonal transport of radioactively labeled protein in some of the regenerating axons showed a deficit at 21-28 days after the lesion, i.e., during innervation of the tectum. Incorporation of labeled amino acid into protein in the retinal ganglion cells was depressed during the same period, but both the transport and incorporation had returned to normal by 36 days after the lesion. These results, together with the results of the accompanying electrophysiological analysis of the effects of TTX58,59, suggest that TTX treatment interferes with two separate events in regeneration, one occurring soon after the nerve lesion and the other during innervation of the tectum. During at least the first of these events the effect of TTX treatment may be to reduce the number of size of the regenerating axon branches. We propose that the TTX effect may be mediated by a reduction in the axonal transport of certain materials, including gangliosides, nucleosides, or proteins specifically involved in regeneration.
D000818:Animals; D001345:Autoradiography; D001369:Axons / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D006054:Goldfish; D009416:Nerve Regeneration / Q000187:drug effects*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009431:Neural Conduction / Q000187:drug effects; D009900:Optic Nerve / Q000187:drug effects*; D012165:Retinal Ganglion Cells / Q000187:drug effects; D013477:Superior Colliculi / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology*; D014795:Visual Pathways / Q000187:drug effects; D014796:Visual Perception / Q000187:drug effects
D001786:Blood Glucose; D009419:Nerve Tissue Proteins; D013779:Tetrodotoxin