Long-term morphometric stabilization of regenerating retinal ganglion cells in the adult rat

Abstract

Purpose: Adult retinal ganglion cells (RGCs) can regenerate their cut axons within peripheral nerve grafts used to replace the distal optic nerve stump. We examined the long-term stabilization of RGCs by guiding their regenerating axons into different termination areas. Methods: The optic nerve (ON) of adult rats was completely cut intraorbitally and its ocular stump was connected with different visual target areas (cortex, midbrain) or with non-visual areas (e.g. muscle). Control groups consisted of blind ending graft and ON cut without graft. The function of the retina was regularly examined by electroretinography. At one, six and nine months postsurgery RGCs were retrogradely labelled with 4-(4-(didecylamino)styryl)-N-methylpyridinium iodide and examined morphometrically. Regenerating RGCs were categorized into three major classes representing the morphological types I, II and III. Results: Our data show that regenerating RGCs remain stable up to nine months after grafting at the ON, although the numbers of axons are low, that is less than 1%, and this number is not significantly effected by reconnection with targets. However, there are significant quantitatively and morphometrically assessable differences between the experimental groups depending on the tissue the RGCs are connected with visual targets. Regenerating RGCs show the highest stability in morphology if reconnected with visual target tissue. Conclusions: Adult RGCs of the rat can be reconnected with visual centers using a peripheral nerve graft. This reconnection stabilizes the cells at morphological and the retina at functional levels for a long period of time, although it does not significantly increase cell survival.