Guidance Molecules in Retinal Axon Regeneration

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DESCRIPTION (provided by applicant): Vision is one of our important senses and plays a central role in much of our behavior. The ability of the adult visual system to convert light information into conscious perception is due to highly organized neural connections between the retina and central nervous system (CNS) targets. These specific connections are formed during embryonic development as nerve cell processes called axons emerge from the retina and navigate within the embryonic brain to find their way to appropriate targets. This path finding involves receptor proteins on axon tips that sense guidance molecules present in the surrounding environment. The sensing of guidance molecules causes retinal axons to speed up, slow down, or change their direction of growth. This remarkable ability of the embryonic visual system to assemble itself is lost in the adult animal where retinal axon injury from trauma or disease often leads to permanent visual disability. In preliminary work, we have discovered that a number of axon guidance molecules, normally present in the embryonic optic nerve, are found in the adult nerve after injury. In this proposal, we test the hypothesis that axon guidance molecules and receptors originally involved in optic nerve development are re-expressed in the injured adult nerve. Furthermore, these guidance molecules play a role in regenerative failure after injury to the visual system by influencing the ability of adult retinal axons to grow. The proposed studies will more fully identify the retinal axon guidance molecules found in the injured optic nerve and characterize whether they have inhibitory or stimulatory effects on adult axon growth. In addition, we will investigate methods to modify these responses and perform in vivo studies to define the functional role of axon guidance molecules after optic nerve injury. Together, these studies will help establish a foundation for developing strategies to promote retinal axon regeneration and functional recovery after injury and disease.