Integrin Activation and Focal Adhesion Kinase in the Survival and Regeneration of Injured Adult Rat CNS Neurons

The retina develops as an outpouching of the diencephalon, and retinal ganglion cells (RGCs) are central nervous system (CNS) neurons whose axons form the optic nerve and extend into the brain. The retina provides an excellent model to study diseases affecting both RGCs and other CNS neurons. Integrin attachment to the extra-cellular matrix (ECM) provides developmental, survival, differentiation and axon extension cues to RGCs which are suspected to be dependent on focal adhesion kinase (FAK) activation. Damage to the optic nerve induces RGC apoptosis and release matrix metallo-proteinases (MMPs) to degrade the ECM and arrest pro-survival signals. This work demonstrates that MMP activation and reduced FAK activity occur early in the apoptotic process and that by respectively reducing and increasing their activity we are able to rescue significant amounts of RGCs, and increase the number of regenerating axons following optic nerve transection.M.Sc