Regenerating optic axons restore topography after incomplete optic nerve injury

Abstract

Following complete optic nerve injury in a lizard, Ctenophorus ornatus, retinal ganglion cell (RGC) axons regenerate but fail to restore retinotectal topography unless animals are trained on a visual task (Beazley et al. [ 1997] J Comp Neurol 370:105-120, [2003] J Neurotrauma 20:1263-1270). Here we show that incomplete injury, which leaves some RGC axons intact, restores normal topography. Strict RGC axon topography allowed us to preserve RGC axons on one side of the nerve (projecting to medial tectum) while lesioning those on the other side (projecting to lateral tectum). Topography and response properties for both RGC axon populations were assessed electrophysiologically. The majority of intact RGC axons retained appropriate topography in medial tectum and had normal, consistently brisk, reliable responses. Regenerate RGC axons fell into two classes: those that projected topographically to lateral tectum with responses that tended to habituate and those that lacked topography, responded weakly, and habituated rapidly. Axon tracing by localized retinal application of carbocyanine dyes supported the electrophysiological data. RGC soma counts were normal in both intact and axotomized RGC populations, contrasting with the 30% RGC loss after complete injury. Unlike incomplete optic nerve injury in mammals, where RGC axon regeneration fails and secondary cell death removes many intact RGC somata, lizards experience a "win-win" situation: intact RGC axons favorably influence the functional outcome for regenerating ones and RGCs do not succumb to either primary or secondary cell death.

Restoration of Visual Function by Enhancing Conduction in Regenerated Axons

“…Based on previous findings that task-specific training might facilitate the establishment of functional topographic mapping (Dunlop et al, 2007), it will be interesting to test whether other accessory rehabilitative training might further enhance functional recovery.…”

Tail regeneration in Lepidosauria as an exception to the generalized lack of organ regeneration in amniotes

“…It has been suggested these interneurons belong to the intraspinal “central locomotor generator,” and are responsible for restoring the movements of hindlimbs (Alibardi, 2014b, 2014c). Finally the optic nerve (Dunlop et al, 2007; Williams, 2017) and also the brain cortex of lizards (Lopez‐Garcia et al, 2002; Minelli, Del Grande, & Manbelli, 1978) have shown remarkable capacity to recover and regenerate neurons and parts of the lost nervous tissues. The latter examples suggests that the ectothermic status of lizards, where the adaptive immune system operates less efficiently and inconstantly in comparison to endotherms while the innate immunity is at work, favors recovery and regeneration.…”

Screening Genes Related to Development and Injury of the Mouse Optic Nerve by cDNA Microarrays

“…Optic-nerve transaction or eyeball enucleation has long been used as a model for studies on CNS injury and regeneration (Ananthakrishnan et al 2008;Dunlop et al 2007). Many studies show that the superior colliculus (SC) undergoes a prominent morphological and molecular reaction after monocular enucleation.…”