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Eldon E Geisert, Joe Caron, XiangDi Wang, GLaucoma; SOX11 Marks Injured Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2396. doi: https://doi.org/.
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The ganglion cell pathways triggered by injury to the eye and biomarkers that reflect the activation of these pathways are largely unknown. The present study defines a biomarker for injury in retinal ganglion cells of the mouse.
Optic nerve crush and blast injury procedures were used to damage retinal ganglion cells in C57Bl/6 mice. The distribution of SOX11 was determined using indirect immunohistochemical methods and the levels of SOX11 protein expression was defined by semi-quantitative immunoblot method. In Situ hybridization was performed using the Affymetrix 2-plex Quantigene View RNA In Situ Hybridization Tissue Assay System. The datasets of GeneNetwork.org were used extensively to examine levels of gene expression in the retina and eye.
Using our normal retina and optic nerve crush databases on GeneNetwork (genenetwork.org), we identified genes that were dramatically upregulated following optic nerve crush. One gene (Sox11) was upregulated approximately 8-fold 2 days after optic nerve crush and appeared to be a prime candidate for a marker of retinal injury. In the normal retina there is a very light immunostaining for SOX11 in retinal ganglion cells and cells in the inner nuclear layer. After optic nerve crush the intensity of staining increases dramatically in only the retinal ganglion cells. A similar increase in staining within the ganglion cells occurs following blast injury to the eye. Our immunoblot analysis also revealed an increase in SOX11 protein in the retina following optic nerve crush. In situ hybridization demonstrated a similar distribution of message for Sox11 in the normal retina as well as a profound increase in Sox11 message within the ganglion cells following optic nerve crush.
SOX11 is implicated in the early injury response of the neural retina to injury. SOX11 protein and Sox11 mRNA are both found in higher concentrations within ganglion cells of the inner retina two days after optic nerve crush. SOX11 protein is found in higher concentration within the neural retina after selective blast injury to the eye. Taken together these data indicate that Sox11 is a good marker for retinal ganglion cell injury and that it may play a role in the initial response of the ganglion cell to axonal damage.
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