The glial cell reaction both in degenerating and regenerating adult rat opt
ic nerve was studied by immunohistochemistry and electron microscopy. Degen
eration in the optic nerve was achieved by complete transection, and the re
tinal stump was then analyzed. The regeneration was observed by autotranspl
antation of a sciatic nerve segment to the transected retinal stump. In bot
h cases, optic nerve axons were labeled anterogradely with rhodamine, follo
wed by immunohistochemical staining. Glial fibrillary acidic protein-positi
ve astrocytes covered the transected end of degenerating optic nerve, where
as in the regenerating optic nerve they enwrapped axonal bundles emerging f
rom the optic nerve stump and migrated together into the transitional zone
intervening between the retinal stump and graft. In electron microscopy, di
rect attachment of astrocyte and Schwann cell was found within the transiti
onal zone, whereby these cells were holding axone between them. Decrease of
04 immunoreactivity, which labels oligodendrocytes, was apparent in the tr
ansected end of retinal stump during the regeneration. The ED1-positivity,
which labels microglia/macrophages, was found in cells accumulated in the t
ransitional 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 periph
eral nerve graft and guide the regenerating axons in cooperation with Schwa
nn cells. The response of oligodendrocytes and microglia/macrophages may al
so be modulated by peripheral nerve. (C) 1999 Elsevier Science Inc.