AUTHOR=Li Ying , Struebing Felix L. , Wang Jiaxing , King Rebecca , Geisert Eldon E. 

TITLE=Different Effect of Sox11 in Retinal Ganglion Cells Survival and Axon Regeneration

JOURNAL=Frontiers in Genetics

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2018.00633

DOI=10.3389/fgene.2018.00633

ISSN=1664-8021

ABSTRACT=<p><bold>Purpose:</bold> The present study examines the role of <italic>Sox11</italic> in the initial response of retinal ganglion cells (RGCs) to axon damage and in optic nerve regeneration in mouse.</p><p><bold>Methods:</bold> Markers of retinal injury were identified using the normal retina database and optic nerve crush (ONC) database on GeneNetwork<sup>2</sup> (<ext-link ext-link-type="uri" xlink:href="http://www.genenetwork.org" xmlns:xlink="http://www.w3.org/1999/xlink">www.genenetwork.org</ext-link>). One gene, <italic>Sox11</italic>, was highly upregulated following ONC. We examined the role of this transcription factor, <italic>Sox11</italic>, following ONC and optic nerve regeneration in mice. <italic>In situ</italic> hybridization was performed using the Affymetrix 2-plex Quantigene View RNA <italic>In Situ</italic> Hybridization Tissue Assay System. <italic>Sox11</italic> was partially knocked out by intravitreal injection of AAV2-CMV-Cre-GFP in <italic>Sox11</italic><sup>f/f</sup> mice. Optic nerve regeneration model used <italic>Pten</italic> knockdown. Mice were perfused and the retinas and optic nerves were dissected and examined for RGC survival and axon growth.</p><p><bold>Results:</bold><italic>Sox11</italic> was dramatically upregulated in the retina following ONC injury. The level of <italic>Sox11</italic> message increased by approximately eightfold 2 days after ONC. <italic>In situ</italic> hybridization demonstrated low-level <italic>Sox11</italic> message in RGCs and cells in the inner nuclear layer in the normal retina as well as a profound increase in <italic>Sox11</italic> message within the ganglion cells following ONC. In <italic>Sox11</italic><sup>f/f</sup> retinas, partially knocking out <italic>Sox11</italic> significantly increased RGC survival after ONC as compared to the AAV2-CMV-GFP control group; however, it had little effect on the ability of axon regeneration. Combinatorial downregulation of both <italic>Sox11</italic> and <italic>Pten</italic> resulted in a significant increase in RGC survival as compared to <italic>Pten</italic> knockdown only. When <italic>Pten</italic> was knocked down there was a remarkable increase in the number and the length of regenerating axons. Partially knocking out <italic>Sox11</italic> in combination with <italic>Pten</italic> deletion resulted in a fewer regenerating axons.</p><p><bold>Conclusion:</bold> Taken together, these data demonstrate that <italic>Sox11</italic> is involved in the initial response of the retina to injury, playing a role in the early attempts of axon regeneration and neuronal survival. Downregulation of <italic>Sox11</italic> aids in RGC survival following injury of optic nerve axons, while a partial knockout of <italic>Sox11</italic> negates the axon regeneration stimulated by <italic>Pten</italic> knockdown.</p>