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tectal tissue implanted into optic tract lesions supports adult RGC axon
regrowth to some extent ( Harvey & Tan, 1992 ), presumably as a
consequence of release of target-based neurotrophic support. Within the
brain, it is often necessary to provide a biocompatible scaffold to support
cellular ingrowth and through which axons can regrow. Hydrogels,
which are hydrophilic polymer-based macromolecular networks swollen
in water, have been used in a number of optic tract injury studies. These
gels can be modified to incorporate signaling peptides or amino sugars
( Plant, Woerly, & Harvey, 1997 ), as well as cells expressing neurotrophic
factors ( Loh, Woerly, Bunt, Wilton, & Harvey, 2001; Plant, Harvey, &
Chirila, 1995 ). In the Loh et al. (1997) study, some regrowth of RGC
axons was seen in hydrogels infiltrated with fibroblasts genetically
modified to express CNTF or BDNF. The greatest and most consistent
axonal ingrowth into the implants was seen in hydrogels containing a
mixture of CNTF- and BDNF-expressing cells. In young rats,
implantation of either neurospheres or umbilical cord mesenchymal
stromal cells into the lesioned optic tract preserved RGCs and was
reported to enhance RGC axonal growth ( Hill et al., 2009; Zwart et al.,
2009 ). Both cell types express neurotrophic factors—at least in vitro
including CNTF, NT-3, and BDNF.
What about distal injuries and application of neurotrophic support at the
cell body? In other CNS systems, this type of approach has been tested with
some success (e.g., Ruitenberg et al., 2004 ). We have delivered CNTF
either as recombinant protein or via AAV to the eye contralateral to an optic
tract injury in anesthetized young rats (18-21-days-old). The AAV-CNTF
injections were combined with the implantation of short multiple segments
of PN across a lesion in the optic tract ( J.W.W. Ooi & A.R. Harvey,
unpublished observations). The PN grafts were cell-free sheaths that had
been repopulated ex vivo with Schwann cells ( Hu et al., 2005 ). Retinal pro-
jections were assessed after intravitreal injections of cholera toxin-B (CTB).
Due most likely to substantial variability in the extent of postlesion cavita-
tion and stability of the PN implants, we found no significant differences in
distal RGC axonal
regrowth between animals
injected with either
AAV-CNTF-GFP or control AAV-GFP.
In a separate series of experiments, and using a 2-mm-long blade to uni-
laterally transect most but not all of the left optic tract, intravitreal injection
of rCNTF combined with the cAMP analogue CPT-cAMP ( Cui et al.,
2003 ) into the contralateral eye significantly enhanced postlesion sprouting
of CTB-labeled retinal axons in the SC, assessed 4-5 weeks after the initial
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