Sprouting of axon-like processes from axotomized retinal ganglion cells induced by normal and preinjured intravitreal optic nerve grafts.

The failure of axonal regeneration in the mammalian central nervous system (CNS) is currently attributed to the glial environment of the lesion site which elaborates a multitude of inhibitory factors. Less attention has been paid to the potential of trophic support associated with the CNS, especially in relation to the status of the damaged CNS after an injury has been evoked. Using a grafting paradigm to implant an optic nerve (ON) segment into the vitreous, we have addressed how a prior damage of the ON before grafting influences its ability to stimulate retinal ganglion cells (RGCs) to sprout axon-like processes. Our results showed that a normal noninjured ON implanted intravitreally stimulated sprouting of RGCs, as revealed by sliver staining of the sprouting cells, as well as increasing the number of RGCs which express GAP-43. A prior crush injury of the ON 7 days before its implantation into the vitreous resulted in a significant decrease in its ability to stimulate RGC sprouting when the crush lesion segment was used as the graft, whereas grafts taken from segments proximal and distal to the lesion segment had potencies similar to that of the noninjured graft. Both astrocytes and oligodendrocytes were drastically reduced in number in the lesion segment graft, suggesting their involvement in the secretion of soluble trophic factors that may play a role in the sprouting and regeneration of damaged neurons.