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genetically modified prior to repopulation of the PN segments by transduc-
ing them with lentiviral vectors (LV) encoding different neurotrophic
factors. No direct stimulus was provided to the RGCs in the eye. In sum-
mary, compared to control grafts (LV-GFP), ON-PN grafts containing
Schwann cells transduced with LV-CNTF increased RGC viability and
supported significantly more RGC axonal regeneration ( Hu et al., 2005 ).
Expression of CNTF from fibroblasts incorporated into the PN sheaths
was not successful ( Hu, Cui, et al., 2007 ). The nature of the growth factor
was also important, because grafts containing Schwann cells transduced
with LV-BDNF or LV-GDNF neither increased RGC viability nor
supported RGC regrowth, even though these grafts did support the in-
growth of large numbers of peripheral sensory axons, presumably growing
in from surrounding peripheral structures ( Hu, Arulpragasam, et al., 2007 ).
Thus, CNTF can increase the viability of axotomized RGCs and can pro-
mote RGC axogenesis even when delivered to the periaxonal compart-
ment. In contrast, BDNF enhances adult RGC viability when applied
intraretinally, but fails to support long-distance regeneration when delivered
either to the soma or to the PN graft.
13. AXONAL REGENERATION AND OPTIC TRACT
INJURY STUDIES
Mention was made earlier regarding the location of axotomy relative
to the parent cell body, and how this has a profound influence on the ability
of an injured adult neuron to regenerate an axon. Most modern-day visual
system regeneration studies use the ON, and almost all crush or transect the
nerve within 1-1.5 mm of the eye. After injury at greater distances from the
eye, including after intracranial ON transection, there may be greater RGC
survival but very few if any RGCs regenerate an axon ( Cho & So, 1993;
Doster, Lozano, Aguayo, & Willard, 1991; Harvey et al., 2006 ). Yet,
distal axonal injuries relative to the soma are the most common in the
CNS, especially in injuries to cerebral white matter or to the spinal cord.
A model that approximates such injuries involves a lesion to the optic
tract, just rostral to the SC.
After partial retinal or ON injuries, plasticity of RGC terminals in the
adult rat SC has been reported ( Kreutz et al., 2004; Tropea et al., 2003 ),
and in the former study, sprouting was enhanced by either intraocular or
tectal delivery of BDNF. We have used various approaches in an attempt
to elicit RGC axonal regrowth after distal optic tract injuries. Fetal rat
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