July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
The Role of MEF2 transcription factors in retinal ganglion cell survival and axon regeneration
Author Affiliations & Notes
  • Xin Xia
    Byers Eye Institute, Stanford University, Palo Alto, California, United States
  • Minjuan Bian
    Byers Eye Institute, Stanford University, Palo Alto, California, United States
  • Sahil Shah
    Byers Eye Institute, Stanford University, Palo Alto, California, United States
  • Kun-Che Chang
    Byers Eye Institute, Stanford University, Palo Alto, California, United States
  • Catalina Sun
    Byers Eye Institute, Stanford University, Palo Alto, California, United States
  • Caroline Yu
    Byers Eye Institute, Stanford University, Palo Alto, California, United States
  • Cara Knasel
    Byers Eye Institute, Stanford University, Palo Alto, California, United States
  • Michael Kapiloff
    Byers Eye Institute, Stanford University, Palo Alto, California, United States
  • Jeffrey L Goldberg
    Byers Eye Institute, Stanford University, Palo Alto, California, United States
  • Footnotes
    Commercial Relationships   Xin Xia, None; Minjuan Bian, None; Sahil Shah, None; Kun-Che Chang, None; Catalina Sun, None; Caroline Yu, None; Cara Knasel, None; Michael Kapiloff, None; Jeffrey Goldberg, None
  • Footnotes
    Support  NEI R01-EY026766 and P30-EY026877, and Research to Prevent Blindness, Inc.
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4845. doi:https://doi.org/
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      Xin Xia, Minjuan Bian, Sahil Shah, Kun-Che Chang, Catalina Sun, Caroline Yu, Cara Knasel, Michael Kapiloff, Jeffrey L Goldberg; The Role of MEF2 transcription factors in retinal ganglion cell survival and axon regeneration. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4845. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : What is the function of myocyte enhancer factor 2 (MEF2) signaling pathways in retinal ganglion cell (RGC) survival and axon regeneration following axon injury? MEF2A and MEF2D are the primary MEF2 isoforms expressed in RGCs and other retinal neuronal cell types. It was recently reported MEF2A knockout enhances RGC survival. Here we explore MEF2 isoforms and point mutants in RGC survival and axon regeneration in vivo.

Methods : We subjected conditional mef2a/c/d triple knockout, mef2a/d double knockout and mef2d knockout mice to optic nerve crush to study MEF2’s effects on neuron protection and regeneration. In some experiments, AAV expression vectors for flag-tagged wildtype and mutant MEF2D proteins were intravitreally injected into the eyes of mef2a/d double knockout mice. Expression of gene and protein were detected by quantitative PCR, immustaining and western blot.

Results : Mef2a/c/d triple knockout and mef2a/d double knockout, but not mef2d knockout alone, increased RGC survival after ONC but showed no change in axon regeneration. On the mef2a/d double knockout background, MEF2D wildtype and mutant proteins didn’t show any pro-survival function, except MEF2D S444A mutant improved axon growth after optic nerve crush in vivo which was consistent with our previous in vitro work showing this activating mutation promoted neurite extension in primary neurons.

Conclusions : Depletion of MEF2 transcriptional regulatory genes, and probably mainly MEF2A, increases RGC survival, whereas MEF2D S444A mutant proteins enhance axon regeneration in vivo.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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