Evidence
for functional regeneration of the pathway in adult rats
Solon Thanos (D-Münster)
Department of Experimental Ophthalmology, School of Medicine, University of Münster, Domagkstraße 15, D-48149 Münster, Germany
Mature
nerve cell axons do not spontaneously regrow within their natural environment
unless they are stimulated by external application of growth-promoting
measures. In the present study, axonal regrowth and restoration of visual
function was studied in adult rats. The optic nerve was completely cut,
and its proximal and distal stumps were realigned and sutured back together.
During the same surgical procedure, the lens was lesioned in order to
induce secondary intraocular inflammation, which is known to strongly
support the survival of retinal ganglion cells (RGCs) and to promote axonal
regeneration within the distal segment of the optic nerve. It appeared
that cut axons grew within the preformed visual pathway to reach central
thalamic and midbrain areas of termination about 5 weeks after lesioning.
Functional restoration of visual reflexes was assessed as response to
illumination with bright light. Responsiveness of the pupil to light was
restored 5 weeks after injury, thus indicating reinnervation of the pretectal
nuclei. Restoration of the ascending pathway between retina and visual
cortex was assured by recording visual evoked potentials (VEPs). As expected,
no VEPs could be recorded during the postsurgical period of axonal growth
throughout the optic nerve and tract. VEPs could be recorded after two
months indicating that synaptic transmission in higher visual areas was
established. The neuroanatomical data show, that cut axons can regenerate
over long distances within the white matter of a central nerve like the
adult optic nerve, spanning over 11 mm to the chiasm and between 12 and
15 mm to the thalamus and midbrain. The recording findings and the restoration
of pupillary responses suggest, for the first time, that lentogenic stimulation
of RGCs is sufficient to induce the formation of growth cones that can
override putative inhibitors at the site of injury. Once formation of
growth cones is successful, they can follow the preformed visual pathway
and form functional synaptic connections within multiple central relays.
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