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Journal of Neuroscience, Vol 8, 265-280, Copyright © 1988 by Society for Neuroscience
Influences of peripheral nerve grafts on the survival and regrowth of axotomized retinal ganglion cells in adult rats
MP Villegas-Perez, M Vidal-Sanz, GM Bray and AJ Aguayo
Neurosciences Unit, Montreal General Hospital, Quebec, Canada.
To investigate the role of extrinsic influences on the survival and growth
of axotomized retinal ganglion cells (RGCs) in the mature mammalian CNS,
both optic nerves (ONs) of adult rats were transected intraorbitally and,
on one side, replaced by an autologous segment of peripheral nerve (PN)
that had been left unconnected distally. The survival of RGCs and the
regrowth of their cut axons into the PN grafts were assessed using
morphometric techniques, neuroanatomic tracers, and immunologic cell
markers to identify and count RGCs at times ranging from 15 d to 9 months.
It was observed that (1) in the absence of a PN graft, more than 90% of the
RGCs died by 1 month after axotomy; (2) between 1 and 3 months after
axotomy, survival of RGCs in the PN- grafted retinas was enhanced 2-4-fold;
(3) nearly 20% of the surviving RGCs regrew lengthy axons into the grafts;
and (4) although the density of surviving RGCs in PN-grafted retinas
decreased significantly between 1 and 3 months after axotomy, the densities
of RGCs with axons extending into the graft remained relatively stable.
These results confirm that in the adult rat retina, neuronal death is a
major effect of axotomy near the cell soma. Although such lesions lead to
the degeneration of many RGCs, we show that extrinsic influences introduced
by the apposition of a PN segment at the time of severing the ON can rescue
a substantial number of these neurons. Because the enhanced survival of
many axotomized RGCs in the PN-grafted retinas appears to be limited to the
first few weeks after injury, while those of RGCs that regenerate axons
into the grafts do not show a parallel decline, it is possible that, in
these experiments, neuronal viability depends on a spectrum of differently
timed influences that may include the early diffusion of critical molecules
arising from the graft and the subsequent establishment of more complex
interactions with graft components.
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