The effect of intraocular tetrodotoxin on the postnatal reduction in the numbers of optic nerve axons in the rat.

We have examined the effects of blocking retinal ganglion cell activity with the sodium channel blocker tetrodotoxin (TTX) on the postnatal reduction in the number of optic nerve axons (and, by interference, the degree of ganglion cell loss in the retina). TTX was injected every other day into the left eyes of a series of albino rats beginning on the day of birth, continuing through the 3rd, 7th, 12th or 14th days when the animals were killed and the optic nerves from both eyes were prepared for electron microscopy. The numbers of axons in the TTX treated and untreated optic nerves from the opposite side were determined from electron micrographs, and compared to the number seen in normal rats at the same ages. Both the magnitude and the time course of the reduction in the number of axons in the TTX-treated and untreated nerves were found to be similar to those seen in normal animals. However, there was a slight reduction in the loss of optic axons in the untreated nerves on the side opposite the TTX injections; this attenuation in axon loss could be mimicked by large systemic injections of TTX, and is probably attributable to a general systemic effect following repeated intraocular injections. These findings indicate that blocking ganglion cell activity with intraocular injections of TTX has little effect on the normal rate of axon loss from the optic nerve and on the numbers of ganglion cells that die during the first two weeks of postnatal life.