Influence of peripheral nerve grafts on the expression of GAP-43 in regenerating retinal ganglion cells in adult hamsters

Abstract

We have examined the ability of axotomized retinal ganglion cells in adult hamsters, to regenerate axons into a peripheral nerve graft attached to the optic nerve and the expression of GAP-43 by these neurons. We also examined the effect on these events of transplanting a segment of peripheral nerve to the vitreous body. The left optic nerves in three groups of hamsters were replaced with a long segment of peripheral nerve attached to the proximal stump of the optic nerve approximately 2 mm from the optic disc to induce regeneration of retinal ganglion cells into the peripheral nerve. An additional segment of peripheral nerve was transplanted into the vitreous of the left eye in the second group. The animals from the first and second groups were allowed to survive for 1-8 weeks and the number of regenerating retinal ganglion cells was determined by applying the retrograde tracer, Fluoro-Gold to the peripheral nerve graft and the expression of GAP-43 was studied by immunocytochemistry in the same retinas. As a control, a segment of optic nerve was transplanted into the vitreous body of the left eye in the third group of hamsters. These animals were allowed to survive for 4 weeks and the number of regenerating retinal ganglion cells was counted as in Groups 1 and 2. The percentages of the regenerating retinal ganglion cells which also expressed GAP-43 were very high at all time points in Group 1 (with no intravitreal peripheral nerve) and Group 2 (with intravitreal peripheral nerve) and at 4 weeks for the Group 3 (with intravitreal optic nerve) animals. In addition, the number of regenerating retinal ganglion cells, the number of retinal ganglion cells expressing GAP-43 and the number of regenerating retinal ganglion cells which also expressed GAP-43 were much higher in Group 2 than in Group 3 at all the time points and it was also much higher in Group 2 than in Group 3 at 4 weeks whereas there was no significant difference between the results from Groups 1 and 3 at 4 weeks. These data suggested that there was a close correlation between the number of the axotomized retinal ganglion cells regenerating axons into the peripheral nerve graft attached to the optic nerve and the expression of GAP-43. In addition, the intravitreal peripheral nerve, probably by releasing various neurotrophic factors and by acting synergistically, can enhance the expression of GAP-43 in some of the axotomized retinal ganglion cells and promote the regeneration of retinal ganglion cells into the peripheral nerve graft.