Funding outcome

Müller glia are crucial cells in retinal metastasis and neurogenesis. From preliminary data, these glia express the polysialic acid N-acetylneuraminic acid (Neu5Ac, Carr, unpublished data). Polysialic acids (polysia) are chain-linked sialic acids that play a role in many biological functions, such as cell-cell signalling. Neu5Ac is a common vertebrate polysia and the only polysia humans express. Müller glia localize around retinal injuries, and our proposed research will investigate if administering 8-keto-Neu5Ac (8-keto) to Xenopus laevis tadpoles will disrupt their ability to regenerate photoreceptors after physical retinal trauma. We hypothesize that if 8-keto blocks Neu5Ac from elongating normally, the function of NCAM, a membrane protein in retinal cells, will be limited, and this will inhibit the efficiency of Müller glial migration to the site of injury and induce retinal regeneration. Our methodology entails raising X. laevis tadpoles and then puncturing a hole in their retina with a needle. After allowing the tadpoles to recover in varying concentrations of 8-keto and housing water for 1 to 2 weeks, our lab will fix the tadpoles and cryosection their retinal tissue. Lastly, GFP-EndoN will label the polysia of Müller glia in fluorescence histochemistry, and software programs will quantify the number of photoreceptors in the repaired retina. The results from this research will allow us to understand better how Müller glia use polysialic acid to repair the retina during early development in X. laevis when retinal neuroplasticity is highest. Although not to the same extent, the human retina does not fully develop until late teens to mid-20s, which may suggest that we possess retinal plasticity during childhood. We anticipate that the results from this study will allow us to further our understanding of the role of polysia in the mechanism of retinal regeneration, and hope to innovate novel approaches for regenerative medicine treating retinopathies.