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Journal of Neuroscience, Vol 10, 2176-2189, Copyright © 1990 by Society for Neuroscience
Basic fibroblast growth factor: receptor-mediated internalization, metabolism, and anterograde axonal transport in retinal ganglion cells
IA Ferguson, JB Schweitzer and EM Johnson Jr
Department of Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110.
Basic fibroblast growth factor (bFGF) was radiolabeled and used in axonal
transport studies to determine whether certain neuronal populations express
functional receptors for bFGF. Unlike 125I-NGF, 125I-bFGF was not
retrogradely transported in the adult rat sciatic nerve or from iris to
trigeminal ganglion or superior cervical ganglion. However, after
intraocular injection of 125I-bFGF into the posterior chamber of the eye of
adult rats, radioactivity was detected within the retinal ganglion cell
projections. This radioactivity was localized to the ipsilateral optic
nerve and in the contralateral lateral geniculate body and the
contralateral superior colliculus by using autoradiographic techniques.
Direct measurement of the radioactivity in dissected brain regions was used
to study the process of 125I-bFGF uptake and transport by retinal ganglion
cells. The uptake and transport were specific for biologically active bFGF
since neither denatured, biologically inactive 125I-bFGF nor 125I-NGF was
taken up and transported. The uptake and transport of 125I-bFGF were
saturable phenomena since they were blocked in the presence of excess,
unlabeled bFGF. Wheat germ agglutinin, but not heparinase, blocked uptake
and transport of 125I-bFGF, a finding that is consistent with the uptake
being mediated by high-affinity bFGF receptors. Radioactivity from 125I-
bFGF was transported in retinal ganglion cell axons in an anterograde
direction at a maximum rate in excess of 1.7 mm/hr. No specific retrograde
transport of bFGF to the retina was detected after 125I-bFGF was injected
into the superior colliculus. The radioactivity from 125I- bFGF that
accumulated in the superior colliculus was lost from this tissue with a
half-life of about 22 hr. Autoradiography of proteins separated by SDS-PAGE
demonstrated that 125I-bFGF was not substantially degraded in the retina
after internalization within retinal ganglion cells. During anterograde
transport, however, 125I-bFGF underwent limited proteolytic cleavage
resulting in 3 prominent 125I-bFGF derivatives of molecular weights greater
than 7000 Da. Although these were the major radioactive species recovered
from the superior colliculus after intraocular injection, some intact
125I-bFGF was also detected within the innervated target. These results
indicate that retinal ganglion cells express high-affinity receptors for
bFGF, that these receptors mediate the internalization of bFGF, that
internalized bFGF undergoes limited proteolytic cleavage, and that bFGF and
its derivatives are anterogradely transported to the lateral geniculate
body and the superior colliculus. These data raise the possibility that
bFGF or its derivatives may act as an anterograde trophic factor in the
visual system, a system that is known to undergo anterograde transneuronal
cell death.
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