Axonal regeneration of retinal ganglion cells (RGCs) into a
normal or pre-degenerated peripheral nerve graft after an optic
nerve pre-lesion was investigated. A pre-lesion performed 1–2
weeks before a second lesion has been shown to enhance axonal
regeneration in peripheral nerves (PN) but not in optic nerves
(ON) in mammals. The lack of such a beneficial pre-lesion effect
may be due to the long delay (1–6 weeks) between the two
lesions since RGCs and their axons degenerate rapidly 1–2
weeks following axotomy in adult rodents. The present study
examined the effects of the proximal and distal ON pre-lesions
with a shortened delay (0–8 days) on axonal regeneration
of RGCs through a normal or pre-degenerated PN graft. The ON
of adult hamsters was transected intraorbitally at 2 mm (proximal
lesion) or intracranially at 7 mm (distal lesion) from the optic
disc. The pre-lesioned ON was re-transected at 0.5 mm from the
disc after 0, 1, 2, 4, or 8 days and a normal or a pre-degenerated
PN graft was attached onto the ocular stump. The number of RGCs
regenerating their injured axons into the PN graft was estimated
by retrograde labeling with FluoroGold 4 weeks after grafting.
The number of regenerating RGCs decreased significantly when
the delay-time increased in animals with both the ON pre-lesions
(proximal or distal) compared to control animals without an
ON pre-lesion. The proximal ON pre-lesion significantly reduced
the number of regenerating RGCs after a delay of 8 days in
comparison with the distal lesion. However, this adverse effect
can be overcome, to some degree, by a pre-degenerated PN graft
applied 2, 4, or 8 days after the distal ON pre-lesion enhanced
more RGCs to regenerate than the normal PN graft. Thus, in order
to obtain the highest number of regenerating RGCs, a
pre-degenerated PN should be grafted immediately after an ON
lesion.
Lentiviral-mediated transfer of CNTF to schwann cells within reconstructed peripheral nerve grafts enhances adult retinal ganglion cell survival and axonal regeneration
