Biology Reference
In-Depth Information
increase in the proapoptotic protein Bax, prolongs RGC survival
substantially (
Isenmann & Bahr, 1997; Malik et al., 2005
). Yet although
overexpression of Bcl-2 provides long-term protection for RGCs, it does
not promote regeneration (
Chierzi et al., 1999
) or augment the effects of
treatments that do (
Inoue, Hosokawa, Morigiwa, Ohashi, & Fukuda,
2002
). Inhibiting either the constitutive or inducible form of the enzyme
nitric oxide synthase (nNOS, iNOS) increases RGC survival two- to
threefold 2 weeks after optic nerve lesion, but again, cells continue to die
(
Koeberle & Ball, 1999
). Reactive oxygen species begin to appear within
24 h of optic nerve injury and peak by 4-5 days (
Kanamori, Catrinescu,
Kanamori, et al., 2010
). Eliminating superoxide radicals by administering
pegylated superoxide dismutase delays RGC death but again does not
prevent it (
Kanamori, Catrinescu, Mahammed, Gross, & Levin, 2010
).
Inhibiting voltage-gated K channels, which is required early in apoptosis
to cause cell shrinkage, likewise transiently decreases RGC death
following axotomy (
Koeberle, Wang, & Schlichter, 2010
). Trophic
factors, including BDNF, GDNF, neurturin, and neurotrophins-4/5, also
transiently promote RGC survival (
Mansour-Robaey, Clarke, Wang,
Bray, & Aguayo, 1994; Mey & Thanos, 1993
), although BDNF
antagonizes the effect of intraocular inflammation on axon regeneration
(
Pernet & Di Polo, 2006
). Finally, deleting the
pten
gene strongly
promotes RGC survival as well as axon regeneration (
Park et al., 2008
),
consistent with the known importance of the PI3K/Akt pathway for
both (
Vaillant et al., 1999
). Intraocular inflammation added to
pten
gene
deletion enhances RGC survival even further (
de Lima et al., 2012
).
7. PARTIAL RETURN OF SIMPLE VISUAL BEHAVIORS
The ability of RGCs to regenerate axons back to their appropriate tar-
get areas raises the question of whether this regeneration results in any func-
tional improvements. Evidence from a recent study indicates that this may
be the case. By 10 weeks after optic nerve injury, mice that regenerate axons
from the eye to the brain show some evidence of improvement in their abil-
ity to entrain daily activity patterns to the ambient day-night cycle, avoid the
deep end of a visual cliff, and track rotating stripes in an optomotor apparatus
(
de Lima et al., 2012
). Performance improved gradually on tests that were
carried out repeatedly over the course of the study but never attained normal
levels (
Fig. 6.5
). Some of these behaviors may require very modest rein-
nervation of central target areas, and it is not yet known whether more
