The glial cell reaction both in degenerating and regenerating adult rat optic nerve was studied by immunohistochemistry and electron microscopy. Degeneration in the optic nerve was achieved by complete transection, and the retinal stump was then analyzed. The regeneration was observed by autotransplantation of a sciatic nerve segment to the transected retinal stump. In both cases, optic nerve axons were labeled anterogradely with rhodamine, followed by immunohistochemical staining. Glial fibrillary acidic protein-positive astrocytes covered the transected end of degenerating optic nerve, whereas in the regenerating optic nerve they enwrapped axonal bundles emerging from the optic nerve stump and migrated together into the transitional zone intervening between the retinal stump and graft. In electron microscopy, direct attachment of astrocyte and Schwann cell was found within the transitional zone, whereby these cells were holding axons between them. Decrease of 04 immunoreactivity, which labels oligodendrocytes, was apparent in the transected end of retinal stump during the regeneration. The ED1-positivity, which labels microglia/macrophages, was found in cells accumulated in the transitional zone of degenerating optic nerve, whereas during regeneration, ED1-immunoreactive cells were also distributed in the retinal stump. These results suggest that astrocytes, usually considered to interfere with optic nerve regeneration, change their characteristics in the presence of peripheral nerve graft and guide the regenerating axons in cooperation with Schwann cells. The response of oligodendrocytes and microglia/macrophages may also be modulated by peripheral nerve.
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