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Author Notes:

Correspondence: Eldon E. Geisert egeiser@emory.edu

YL, FS, and EG contributed design of this study and drafted the article.

JW performed all ONC procedures and data analysis.

RK was responsible for animal breeding, assisted with all animal surgeries and isolated RNA from samples.

YL performed intravitreal injections and immunostaining.

All authors contributed to manuscript revision, read and approved the submitted version.

We thank Steven G. Hart and XiangDi Wang for their early technical work on this project.

We also thank Rafi Ahmed and Ali Ellebedy from Department of Microbiology and Immunology in Emory University for giving Sox11f/f mice as a gift.

We thank Veronique Lefebvre at Cleveland Clinic who originally created the Sox11f/f mice.

We also thank Fred Gage for the AAV-Cre-GFP vector.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Subjects:

Research Funding:

This work was supported by DoD Grant W81XWH-12-1-0255 from the United States Army Medical Research and Materiel Command and the Telemedicine and Advanced Technology (to EG), Vision Core Grant P030EY006360, and an Unrestricted Grant from Research to Prevent Blindness.

This publication was supported in part by the Emory Integrated Genomics Core (EIGC) Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Genetics & Heredity
  • retinal ganglion cells
  • Sox11
  • optic nerve crush
  • axon regeneration
  • AAV2
  • TRANSCRIPTION FACTOR SOX11
  • OPTIC-NERVE REGENERATION
  • NEUROTROPHIC FACTOR
  • MOUSE MODEL
  • SRY-BOX
  • EXPRESSION
  • GENE
  • GROWTH
  • INJURY
  • MECHANISMS

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

Tools:

Journal Title:

Frontiers in Genetics

Volume:

Volume 9

Publisher:

, Pages 633-633

Type of Work:

Article | Final Publisher PDF

Abstract:

Purpose: The present study examines the role of Sox11 in the initial response of retinal ganglion cells (RGCs) to axon damage and in optic nerve regeneration in mouse. Methods: Markers of retinal injury were identified using the normal retina database and optic nerve crush (ONC) database on GeneNetwork2 (www.genenetwork.org). One gene, Sox11, was highly upregulated following ONC. We examined the role of this transcription factor, Sox11, following ONC and optic nerve regeneration in mice. In situ hybridization was performed using the Affymetrix 2-plex Quantigene View RNA In Situ Hybridization Tissue Assay System. Sox11 was partially knocked out by intravitreal injection of AAV2-CMV-Cre-GFP in Sox11f/f mice. Optic nerve regeneration model used Pten knockdown. Mice were perfused and the retinas and optic nerves were dissected and examined for RGC survival and axon growth. Results:Sox11 was dramatically upregulated in the retina following ONC injury. The level of Sox11 message increased by approximately eightfold 2 days after ONC. In situ hybridization demonstrated low-level Sox11 message in RGCs and cells in the inner nuclear layer in the normal retina as well as a profound increase in Sox11 message within the ganglion cells following ONC. In Sox11f/f retinas, partially knocking out Sox11 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 Sox11 and Pten resulted in a significant increase in RGC survival as compared to Pten knockdown only. When Pten was knocked down there was a remarkable increase in the number and the length of regenerating axons. Partially knocking out Sox11 in combination with Pten deletion resulted in a fewer regenerating axons. Conclusion: Taken together, these data demonstrate that Sox11 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 Sox11 aids in RGC survival following injury of optic nerve axons, while a partial knockout of Sox11 negates the axon regeneration stimulated by Pten knockdown.

Copyright information:

© 2018 Li, Struebing, Wang, King and Geisert.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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