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axon. A naturally occurring mutation in mice, Wallerian degeneration
slow (Wld
S
), is associated with the blockade of this axonal degeneration
program (
Perry, Brown, & Lunn, 1991
) and demonstrates that cell body
death and axonal degeneration programs are distinct. In fact, most of our
knowledge of retinal ganglion cell axonal degeneration derives from this
naturally occurring fusion mutation.
There has been a significant improvement in methods to study axonal
degeneration. Conventional histological or ultrastructural methods using
postmortem tissues provide an excellent static evaluation of axonal degen-
eration, but only at fixed times. Axonal degeneration has been quantitatively
assessed for several days after injury in the spinal cord in the mouse
(
Kerschensteiner, Schwab, Lichtman, & Misgeld, 2005
), in the optic nerve
in the rat (
Knoferle et al., 2010
), and in the saphenous nerve using fibered
fluorescence microscopy (
Vincent et al., 2006
). Real-time imaging of axonal
degeneration in living animals, for example, two-photon excitation micros-
copy of deeply located axons, extends to a depth of 1 mm (
Svoboda &
Yasuda, 2006
). Some of the methods used for these imaging procedures
are invasive because the axons being studied are surgically exposed, with po-
tential confounding by ischemic or traumatic effects on adjacent tissues.
The retina provides a unique platform for noninvasive imaging of CNS
axons. Recent techniques in real-time imaging of axonal degeneration and
axonal transport have provided valuable information on neurodegeneration
(
Kerschensteiner et al., 2005; Misgeld, Kerschensteiner, Bareyre, Burgess, &
Lichtman, 2007; Vincent et al., 2006; Wang & Schwarz, 2009
). Most of
these techniques were first adapted for use on myelinated axons, which
can differ from unmyelinated axons in the mechanism of degeneration
(
Ey, Kobsar, Blazyca, Kroner, & Martini, 2007
).
Given that axonal degeneration is a critical element in the pathophysio-
logy of many neurological diseases (
Coleman & Perry, 2002
) and almost all
optic neuropathies (
Toffoli & Levin, 2010
), our group has taken advantage
of the clarity of the ocular media to directly image degeneration of the un-
myelinated retinal ganglion cell axons coursing within the nerve fiber layer
of the superficial retina. This was done by
in vivo
confocal scanning laser
ophthalmoscopy and allows noninvasive examination of longitudinal
CNS axonal degeneration on both sides of an injury. We demonstrated
the surprising finding that retrograde and Wallerian degeneration of these
unmyelinated retinal ganglion cell axons occurred with a nearly identical
time course and to a similar magnitude (
Kanamori, Catrinescu, Belisle,
Costantino, & Levin, 2012
).
