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

Abstract

<b>Purpose:</b> The present study examines the role of <i>Sox11</i> in the initial response of retinal ganglion cells (RGCs) to axon damage and in optic nerve regeneration in mouse. <b>Methods:</b> Markers of retinal injury were identified using the normal retina database and optic nerve crush (ONC) database on GeneNetwork² (www.genenetwork.org). One gene, <i>Sox11</i>, was highly upregulated following ONC. We examined the role of this transcription factor, <i>Sox11</i>, following ONC and optic nerve regeneration in mice. <i>In situ</i> hybridization was performed using the Affymetrix 2-plex Quantigene View RNA <i>In Situ</i> Hybridization Tissue Assay System. <i>Sox11</i> was partially knocked out by intravitreal injection of AAV2-CMV-Cre-GFP in <i>Sox11</i> ^f/f mice. Optic nerve regeneration model used <i>Pten</i> knockdown. Mice were perfused and the retinas and optic nerves were dissected and examined for RGC survival and axon growth. <b>Results:</b> <i>Sox11</i> was dramatically upregulated in the retina following ONC injury. The level of <i>Sox11</i> message increased by approximately eightfold 2 days after ONC. <i>In situ</i> hybridization demonstrated low-level <i>Sox11</i> message in RGCs and cells in the inner nuclear layer in the normal retina as well as a profound increase in <i>Sox11</i> message within the ganglion cells following ONC. In <i>Sox11</i> ^f/f retinas, partially knocking out <i>Sox11</i> 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 <i>Sox11</i> and <i>Pten</i> resulted in a significant increase in RGC survival as compared to <i>Pten</i> knockdown only. When <i>Pten</i> was knocked down there was a remarkable increase in the number and the length of regenerating axons. Partially knocking out <i>Sox11</i> in combination with <i>Pten</i> deletion resulted in a fewer regenerating axons. <b>Conclusion:</b> Taken together, these data demonstrate that <i>Sox11</i> 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 <i>Sox11</i> aids in RGC survival following injury of optic nerve axons, while a partial knockout of <i>Sox11</i> negates the axon regeneration stimulated by <i>Pten</i> knockdown.