Biology Reference
In-Depth Information
It is unclear whether the synchronous nature of retrograde and
Wallerian degeneration is specific to RGC axons, intraretinal RGC axons,
unmyelinated CNS axons, or even CNS axons. As mentioned previously,
the study of axonal degeneration
in vivo
is highly dependent on imaging
techniques, which in most cases requires exposure of overlying tissue
(
Kerschensteiner et al., 2005; Knoferle et al., 2010; Vincent et al.,
2006
). These differences in technique may explain why synchronous
retrograde and Wallerian degeneration are not commonly recognized.
There are some situations where the proximal and distal axon responses
to axotomy are symmetric. For example,
in vitro
models usually show a
similar rate of degeneration in both directions (
Cengiz, Ozturk,
Erdogan, Him, & Elif, 2010
). The early axonal responses to transection,
that is, calcium wave-dependent calpain activation, depolymerization
of microtubules immediately adjacent to the injury site, and
disorganization of the axonal plasmalemma (
Gitler & Spira, 1998; Spira,
Oren,Dormann,&Gitler,2003;Ziv&Spira,1995
) are symmetric
(
Meiri, Dormann, & Spira, 1983
).
In contrast, retrograde and Wallerian degeneration are normally viewed
as intrinsically asymmetric. Retrograde degeneration involves the proximal
axonal segment, which is contiguity with the cell soma, and Wallerian
degeneration involves the distal segment, which is isolated from the soma. This
means that beyond the presence of axonal injury, retrograde degeneration
involves deprivation of growth factors from the postsynaptic target, while
Wallerian degeneration separates the distal axon from the metabolic support
supplied by the cell body. In the mammalian CNS, where regeneration is
abortive and incomplete (
Giftochristos & David, 1988; Villegas-Perez,
Vidal-Sanz, Bray, & Aguayo, 1988
), proximal axons remain stable for
longer period than distal axons (
Conforti, Adalbert, & Coleman, 2007
).
4. THERAPIES FOR OPTIC NERVE DISEASE
There is a paucity of treatments for optic neuropathies. There are
some for which treatment makes a difference, for example, optic neuritis,
compressive optic neuropathy, and papilledema. In these cases, the visual
loss can be reversed because the axonal damage is relieved before retinal gan-
glion cell death has occurred (
Danesh-Meyer et al., 2008
). In most other
optic neuropathies, such as glaucoma and ischemic optic neuropathy, the
visual loss is permanent, reflecting the fact that severe axonal injury and con-
sequent retinal ganglion cell death are irreversible. Although the progression
