Evidence for functional regeneration of the visual pathway in adult rats

Abstract

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.The neuroanatomical data showed that cut axons can regenerate over long distances within the white matter of a central nerve like the adult optic nerve, spanning over 11mm to the chiasm and between 12 and 15mm to the thalamus and midbrain. Responsiveness of the pupil to light was restored five weeks after injury, thus indicating reinnervation of the pretectal nuclei. Restoration of the ascending pathway between the retina and visual cortex was assured by recording flash visual evoked potentials (FVEPs). As expected, no FVEPs could be recorded during the postsurgical period of axonal growth throughout the optic nerve and tract. FVEPs could be recorded after two months, indicating that synaptic transmission in higher visual areas was established.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.