Mechanisms of axonal elongation during regeneration of adult retinal axons

摘要

Adult retinal ganglion cells (RGCs) exihibit only a limited and transient regenerative sprouting after injury, and they fail to extend axons within the inhospitable interior of the optic nerve. The failure to regenerate axons is attributed to inhibitory proteins associated with myelin and/or the glial scar formed immediately after injuries. Under certain experimental conditions axonal regeneration is possible, and has been examined to understand the mechanisms of regenerative growth. Such conditions include replacement of the distal segment of the cut optic nerve with a peripheral nerve segment injury to the optic lens and growth of axons within their own distal environment and in vitro culture models. Expanding on these models, the mutual mechanisms which trigger de lesio formation of growth cones and support elongation of axons will be discussed. In particular, use of proteomic methods will be first presented to document that axonal regrowth is associated with regulation of certain proteins. A proteomic-genomic correlation will be then presented to link protein-regulation to transcriptomic changes. Identified proteins which seem to play a role in axonal growth have been cloned and used for transfection experiments in order to stimulate growth of axons. The presentation will sum up with novel proteins with a high potential to promote neurite growth and promise its use to manage acute neurodegenerative diseases.