Many recent studies suggest that glial cells help to determine the success or failure of axonal growth in the visual system. It is clear, moreover, that regulatory signals must exist to control the organization of glial environments associated with axonal growth. My laboratory has identified and isolated 4 brain peptides, referred to as Glia-Promoting Factors (GPFs), that stimulate proliferation and differentiation of astroglia or oligodendroglia in culture. The GPFs appear to be important growth factors in injured CNS by altering rates of cellular differentiation, composition of surface molecules, and levels of enzymic activities in specific glial populations. Perhaps GPFs act as glial cell """"""""activators"""""""" and help to organize glial environments that influence axonal growth. I propose to investigate the role of glial constituents upon axonal growth in vitro and in vivo. Specific populations of glia will be isolated and stimulated in culture using purified GPFs and other known glial cell activators. The secretion products and cell surface molecules of these treated glial cultures will be examined for their abilities to enhance or retard retinal ganglion cell growth. Further study of putative axonal-growth regulators will include characterization by gel filtration, ion exchange chromatography, reverse phase high performance liquid chromatography and sodium dodecyl sulphate gel electrophoresis. In addition GPFs and soluble axonal-growth regulators will be injected intracranially and intraocularly to examine what influence activated glia may have upon retinal ganglion cell growth in vivo. Neuronal growth will be followed by monitoring patterns of new protein biosynthesis and by measuring the extent of axonal growth. Perhaps thoughtful characterization of glial-neuronal interactions will lead to new strategies for the treatment of damage in the human visual system.
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