Specificity of a neuronotrophic factor from rabbit corneal epithelial cultures

Previous studies have demonstrated that of the three major cell types of rabbit cornea, only epithelial cells released a neuronotrophic factor that is active in both promoting survival and inducing neurite outgrowth of dissociated trigeminal neurons. In this study, the specificity of neuronotrophic factor production by selected epithelial cell types and the responsiveness of neurons from several different tissues to this trophic factor were determined. Cell cultures of various epithelia and dissociated neurons from several ganglia of neonatal and adult rabbits were utilized. In comparison with adult corneal epithelium, adult bulbar conjunctiva released a similar amount of trophic factor. Neonatal corneal epithelium released five times more, but adult retinal pigment epithelium and neonatal skin epithelium yielded less than a third and one-sixth respectively, and three cell lines (adult skin, kidney and neonatal lens epithelia) released only negligible amounts. Compared with its effect on neonatal trigeminal neurons, the trophic factor from adult corneal epithelium was similarly active on neonatal dorsal root neurons, but only half as effective on adult trigeminal neurons and less than one-tenth as effective on neonatal superior cervical neurons. The effect of nerve growth factor (from mouse submaxillary gland) on these neurons was tested for comparison. The results indicated that of the tissues studied, neuronotrophic factor was released in abundance only from corneal and conjunctival epithelia, and was active predominantly on trigeminal and dorsal root neurons (sensory neurons). This is consistent with the concept that the developmentally regulated release of trophic factor by target cells may be an underlying mechanism for neurogenesis and nerve regeneration.