The effect of intraocular injection of tetrodotoxin on fast axonal transport of [3H]proline- and [3H]fucose-labeled materials in the developing rat optic nerve.
The fast axonal transport of [3H]proline-labeled proteins and [3H]fucose-labeled glycoproteins delivered to the dorsal lateral geniculate nucleus in the developing rat optic nerve was investigated during tetrodotoxin-induced monocular impulse blockade. Repeated intraocular injections of various dosages of tetrodotoxin or citrate buffer vehicle were made every two days in rats aged 5-21 days postnatal, and the accumulation of rapidly transported radioactivity in the lateral geniculate nucleus measured between three and twelve hours post-injection at each age. The effectiveness of prolonged tetrodotoxin treatment was monitored by loss of the pupillary light reflex and the level of cytochrome oxidase activity in the contralateral superior colliculus and dorsal lateral geniculate nucleus. Numbers of optic axons proximal to the chiasm and the frequency of retinal ganglion cells per unit distance from the optic disc were examined for signs of tetrodotoxin-induced degeneration of the retinofugal pathway. Tetrodotoxin-treatment reduced the amount of fucosyl glycoproteins, but not proline-labeled proteins, axonally transported to the lateral geniculate nucleus during the first three weeks of postnatal development. Other studies indicated that tetrodotoxin significantly reduced the incorporation of [3H]fucose into retinal proteins indicating that the reduction in transport was probably due to a decrease in precursor incorporation into retinal ganglion cells. Electron microscopy of ganglion cells at 21 days revealed dilated and vacuolated Golgi cisternae associated with tetrodotoxin treatment, suggesting that tetrodotoxin may alter fucose metabolism by secondarily disrupting Golgi organization. Other protein synthetic machinery in these cells, including ribosomes and rough endoplasmic reticulum, appeared normal throughout tetrodotoxin treatment. These data indicate that Na+-dependent optic impulse activity may be indirectly related to the axonal transport of glycoproteins during early postnatal development by mediating the incorporation of precursor into glycoproteins at the Golgi apparatus and their subsequent entrance into the fast transport system.
R V
RV
Riccio
M A
MA
Matthews
D000818:Animals; D001370:Axonal Transport / Q000187:drug effects*; D005643:Fucose / Q000378:metabolism*; D008854:Microscopy, Electron; D009900:Optic Nerve / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D011392:Proline / Q000378:metabolism*; D051381:Rats; D012160:Retina / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology*
D005643:Fucose; D013779:Tetrodotoxin; D011392:Proline