A neurotrophic activity of adult monkey and bovine interphotoreceptor matrix (IPM) was examined by using cultured human Y79 retinoblastoma cells as a model system. The cells were stimulated for 7 days in suspension culture with soluble IPM components and then attached to poly‐D‐lysine substratum. IPMs from both species induced greater than 80% neuronal differentiation of Y79 cell aggregates after 11 days of attachment as adjudged morphologically by the extension of lengthy, neurite‐like processes. Immunocytochemical studies indicate that differentiated Y79 cells had an increased level of expression of neuron‐specific enolase and a concomitant decreased expression of glial fibrillary acidic protein. This neurotrophic activity cannot be ascribed to nerve growth factor, platelet‐derived growth factor, fibroblast growth factor, epidermal growth factor, or transforming growth factor beta. Although the nature of the factor and its cellular source have yet to be characterized, it may be related to a recently described neurotrophic protein secreted by human fetal retinal pigment epithelial cells in culture. Our findings provide evidence supporting the neuroblastic potential of the Y79 cell line and indicate that the IPM contains a potent neurotrophic activity. Such factors may be important to normal differentiation and maintenance of function of the neural retina.
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