OPTIC-NERVE GLIA SECRETE A LOW-MOLECULAR-WEIGHT FACTOR THAT STIMULATES RETINAL GANGLION-CELLS TO REGENERATE AXONS IN GOLDFISH

The ability of lower vertebrates to regenerate an injured optic nerve has been widely studied as a model for understanding neural developmen t and plasticity. We have recently shown that, in goldfish, the optic nerve contains two molecules that stimulate retinal ganglion cells to regenerate their axons in culture: a low-molecular-weight factor that is active even at low concentrations (axogenesis factor-1) and a somew hat less active polypeptide of molecular weight 10,000-15,000 (axogene sis factor-2). Both are distinct from other molecules described previo usly in this system. The present study pursues the biological source a nd functional significance of axogenesis factor-1. Earlier studies hav e shown that cultured goldfish glia provide a highly favorable environ ment for fish or rat retinal ganglion cells to extend axons. We report that the glia in these cultures secrete high levels of a factor that is identical to axogenesis factor-1 in its chromatographic properties and biological activity, along with a larger molecule that may coincid e with axogenesis factor-2. Axogenesis factor-1 derived from either go ldfish glial cultures or optic nerve fragments is a hydrophilic molecu le with an estimated molecular weight of 700-800. Prior studies have r eported that goldfish retinal fragments, when explanted in organ cultu re, only extend axons if the ganglion cells had been ''primed'' to beg in regenerating in vivo for one to two weeks. However, axogenesis fact or-1 caused the same degree of outgrowth irrespective of whether gangl ion cells had been induced to regenerate new axons in vivo. Moreover, ganglion cells primed to begin regenerating in vivo continued to exten d axons in culture only when axogenesis factor-1 was present. In summa ry, this study shows that glial cells of the goldfish optic nerve secr ete a low-molecular-weight factor that initiates axonal regeneration f rom retinal ganglion cells.