AXONAL-TRANSPORT OF PROTEOGLYCANS IN REGENERATING GOLDFISH OPTIC-NERVE

Labeling of goldfish optic nerve and tectum proteoglycans (PGs) was qu antified following intraocular injection of (SO4)-S-35 and [H-3]prolin e or [H-3]glucosamine. Both intact animals and animals which had survi ved for periods of 10 to 119 days after an optic nerve crush lesion we re examined. Regenerating retinal ganglion cell (RGC) axons reached th e rostral pole of the tectum by 10 days postcrush and by 21 days had d ensely innervated the optic synaptic laminae. If the contralateral tec tum had been removed, the regenerating RGC axons innervated the remain ing ipsilateral tectum with a delay of approximately 14 days. There wa s a biphasic increase in the synthesis and transport of PGs during opt ic fiber regeneration which was not affected by the removal of the tec tum. More highly sulfated PGs were preferentially off-loaded from the orthograde transport pool proximally in the optic nerve, both in the u noperated animals and during regeneration. These PGs also had longer a nd/or more glycosaminoglycan (GAG) chains than those off-loaded distal ly, in the tectum. During early regeneration, the synthesis and transp ort of chondroitin sulfate PGs (CSPGs) increased more than those of he paran sulfate PGs, and during the period of optic fiber invasion of th e synaptic laminae, the PGs retained in the nerve had a higher content of CSPGs than those transported into the tectum. Removal of the contr alateral tectum at the time of nerve crush resulted in a decrease in t he size and/or numbers of GAGs and overall sulfation of PGs in the ner ve by 21 days postoperatively. In addition, in the absence of the tect um, the HS/CS ratio in the nerve remained at preoperative levels until 21 days postoperatively at which time it began to fall. Newly synthes ized PGs transported in the regenerating retinotectal projection under go changes reflecting regulation of transcription/translation and of p ost-translational modification at the level of glycosyltransferase and sulfotransferase activities and by mechanisms intrinsic to the orthog rade and retrograde transport system of RGC axons. These changes are r egulated by both target-dependent and target-independent signals. (C) 1994 Academic Press, Inc.