E587 ANTIGEN IS UP-REGULATED BY GOLDFISH OLIGODENDROCYTES AFTER OPTIC-NERVE LESION AND SUPPORTS RETINAL AXON REGENERATION

The properties of glial cells in lesioned nerves contribute quite subs tantially to success or failure of axon regeneration in the CNS. Goldf ish retinal axons regenerate after optic nerve lesion (ONS) and expres s the L1-like cell adhesion protein E587 antigen on their surfaces. Go ldfish oligodendrocytes in vitro also produce E587 antigen and promote growth of both fish and rat retinal axons. To determine whether glial cells in vivo synthesize E587 antigen, in situ hybridizations with E5 87 antisense cRNA probes and light-and electron microscopic E587 immun ostainings were carried out. After lesion, the goldfish optic nerve/tr act contained glial cells expressing E587 mRNA, which were few in numb er at 6 days after ONS, increased over the following week and declined in number thereafter. Also, E587-immunopositive elongated cells with ultrastructural characteristics of oligodendrocytes were found. Thus, glial cells synthesize E587 antigen in spatiotemporal correlation with retinal axon regeneration. To determine the functional contribution o f E587 antigen, axon-oligodendrocyte interactions were monitored in co -culture assays in the presence of Fab fragments of a polyclonal E587 antiserum. E587 Fabs in axon-glia co-cultures prevented the normal tig ht adhesion of goldfish retinal growth cones to oligodendrocytes and b locked the preferential growth of fish and rat retinal axons on the ol igodendrocyte surfaces. The ability of glia in the goldfish visual pat hway to upregulate the expression of E587 antigen and the growth suppo rtive effect of oligodendrocyte-associated E587 antigen in vitro sugge sts that this L1-like adhesion protein promotes retinal axon regenerat ion in the goldfish. (C) 1998 Wiley-Liss, Inc.