Assessing Axonal Fate, Myelination and Visual Function Recovery after New Gene Treatment

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Retinal ganglion cells (RGCs) are the only neuronal type that relays visual information from the retina to the brain. Like other central nervous system (CNS) axons, RGC axons generally do not regenerate following damage, presenting a major obstacle for treating patients with optic nerve trauma or glaucoma. Previously, using optic nerve crush model, we and others have shown that different genetic interventions induce RGC axon regeneration in adult mice. However, despite the considerable numbers of regenerated axons, recovery of visual function has been limited or non-existent. It is generally viewed that axon regeneration alone is not enough to restore meaningful recovery of visual functions after axonal injury. Evidence indicates that remyelination facilitating saltatory conduction is another key step toward attaining functional restoration. Previously, different groups have reported the extent to which regenerated RGC axons are myelinated in adult mice. However, the results have been variable, raising a possibility that remyelination of RGC axons occurs only under certain conditions. Overall, it is unclear whether there is an optimal intervention for inducing both axon regeneration and remyelination. In this proposal, we will test a hypothesis that manipulating certain genes and treatments will permit both axon regeneration and remyelination. In the first aim, we will determine whether regenerated RGC axons are myelinated in the mice receiving different regenerative treatments. In the second aim, we will determine the degree to myelination is attained with myelinating-promoting treatment. Results obtained from these studies will provide valuable information on developing future therapies to regenerate injured retinal axons after trauma or in diseases.