Biology Reference
In-Depth Information
nonviral gene transfer, for example, by transfecting RGCs by applying the
relevant plasmid DNA attached to a polymer matrix to injured axons (
Berry,
Barrett, Seymour, Baird, & Logan, 2001
) or by using intraocular
nanoparticle delivery for slow release (
Read, Cashman, & Kumar-Singh,
2010; Wadhwa, Paliwal, Paliwal, & Vyas, 2009
). Electroporation has
also been used to introduce exogenous DNA and other molecules into
RGCs; survival of axotomized RGCs was increased after BDNF (
Mo
et al., 2002
) or GDNF plasmid electroporation (
Ishikawa et al., 2005
),
although this increased viability appeared to be transient. These methods
generally have low transfection rates and short-lived transgene expression.
The first issue is problematic but a finite period of trophic support, as will
be seen later, may yet prove advantageous when eliciting regeneration
after neurotrauma.
9. CELLULAR DELIVERY OF NEUROTROPHIC FACTORS
An alternate strategy for delivering neurotrophic factors to RGCs over
a prolonged period, without the need for repeated intraocular injections, is to
implant cells—either as free suspensions or encapsulated in a semipermeable
framework—into the vitreal chamber (
Zanin et al., 2012
). Such an approach
has been used in studies targeting photoreceptors (e.g.,
Emerich & Thanos,
2008; Lawrence et al., 2004; Lund, Ono, Keegan, & Lawrence, 2003;
Sieving et al., 2006
). Suspension injections require attention to possible
immunological effects and possible continuation of cell proliferation
within the eye; encapsulation can minimize such potential complications
although any such implants should not significantly interfere with light
transmission and visual function.
For injured RGCs in the inner retina, effects on survival and axonal
regeneration have been assessed after intravitreal implantation of PN seg-
ments (
Ahmed et al., 2006; Berry, Carlile, & Hunter, 1996
), Schwann cells
(
Maffei, Carmignoto, Perry, Candeo, & Ferrari, 1990
), genetically
modified fibroblasts (
Logan et al., 2006
), or xenogeneic neural tube-
derived stem cells (
Charalambous, Hurst, & Thanos, 2008
). Beneficial
effects of Schwann cells or neural precursor cells are presumably due to the
expression of a range of growth-promoting factors, including neurotrophic
factors such as BDNF and CNTF, as well as adhesion molecules and
other axogenic-promoting factors. Increased RGC viability in animal
models of glaucoma has been documented after intravitreal injection of
BDNF-secreting mesenchymal stem cells (MSCs) (
Harper et al., 2011
).
