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Ying Li, Felix Struebing, Rebecca King, Jiaxing Wang, Eldon Geisert; The Role of Sox11 in Retinal Ganglion Cell Survival and Axon Regeneration. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5506. doi: https://doi.org/.
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The present study examines the role of Sox11 in the initial response of retinal ganglion cells (RGC) to axon damage and optic nerve regeneration in the mouse.
Sox11 and Pten were knocked down by intravitreal injection of AAV2-CMV-Cre-GFP or AAV2-shRNA-Pten-GFP in 4-6-week-old Sox11fl/fl mice. The control group received AAV2-CMV-GFP. Optic nerve crush (ONC) was performed 2 weeks after viral vector injection. 12 days after ONC, Alexa Fluor® 647-conjugated Cholera Toxin B (CTB) was used to label regenerating axons. After 14 days, retinas and full-length optic nerves were dissected. RGCs were labeled with pan-RGC marker RBPMS.
In the retina, knocking down Sox11 in the Sox11fl/fl mice significantly increased RGC survival after ONC as compared to a AAV2-CMV-GFP control group (5,591.6±251.9/mm2 vs. 3,310.0±91.9/mm2, n=4, p<0.05). When Pten was simultaneously knocked down, the RGC survival results were similar. Combinatorial knock-down of both Sox11 and Pten resulted in a significant increase in RGC survival as compared to knocking down Pten only. These data suggest that Sox11 depletion increases RGC survival independent of Pten expression. For axon regeneration, Pten suppression resulted in a significant increase in the number and the length of regenerating axons as compared to: GFP controls, knocking down Sox11 only, or knocking down both Pten and Sox11. Sox11 depletion did not show a significant effect on axonal regeneration as compared to GFP controls.
Knocking down Sox11 aids in RGC survival following injury of optic nerve axons, while it has little effect on the ability of axons to regenerate. However, knocking down Sox11 can negate the regeneration facilitated by knocking down Pten, demonstrating that Sox11 expression is necessary for axonal regeneration. These results must be interpreted cautiously in light of control experiments in which injection of AAV2-CMV-GFP resulted in a significant upregulation of a short isoform of Sox11 (Struebing et al. doi.org/10.3389/fnmol.2017.00354).
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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