Journal of Neuroscience, Vol 3, 2172-2182, Copyright © 1983 by Society for Neuroscience
Retrograde transport of nerve growth factor in lesioned goldfish retinal ganglion cells
HK Yip and EM Johnson Jr
Previous experiments have shown that nerve growth factor (NGF) enhances
regeneration of goldfish optic nerve after local application of NGF at the
site of the lesion. However, the site and mechanism of action of NGF are
not yet known. One possibility is that NGF is taken up at the site of the
lesion and retrogradely transported to the cell bodies of the retinal
ganglion cells and thereby exerts its trophic effects. The present work was
carried out to assess the role of retrograde transport of NGF in this
enhanced regeneration of goldfish retinal ganglion cells. In intact retinal
ganglion cells of the goldfish, 125I-labeled NGF was found not to be
retrogradely transported from the optic tectum to the retina, suggesting
that retinal ganglion cells do not possess specific NGF receptors. However,
if [125I]NGF was injected at the site of an optic nerve lesion at the time
of lesion, [125I]NGF was retrogradely transported from the site of a lesion
of the optic nerve to the cell body of retinal ganglion cells. The
accumulated radioactivity was shown to be intact NGF by SDS-PAGE. The
ability of NGF to decrease the time required for recovery of visual
function was observed only when NGF was administered at the time of the
injury. Likewise, no transport of [125I]NGF was observed when it was
injected at the crush site 16 hr or longer after crush. Thus, there is a
temporal correlation between the ability of intact [125I]NGF to be
retrogradely transported from a lesion site to the retina and the
regenerative effect of NGF. Autoradiography showed that the [125I]NGF
accumulated only in retinal ganglion cells. The transport of NGF in the
lesioned goldfish visual system was not specific for NGF in that other
proteins (cytochrome c, bovine serum albumin) were transported equally
well. Likewise, transport of [125I]NGF was not prevented by concomitant
administration of excess unlabeled NGF. The retrograde transport of
[125I]NGF therefore was not selective and did not appear to be mediated by
specific NGF receptors in this system. This nonspecific transport of
[125I]NGF did not occur in the axotomized spinal motor neurons in the
neonatal or adult rat or in the newt. However, receptor-mediated transport
is seen in lesioned sensory neurons in both species.(ABSTRACT TRUNCATED AT
400 WORDS)