April 2011
Volume 52, Issue 14
ARVO Annual Meeting Abstract  |   April 2011
mTOR Activity Restores Retinal Ganglion Cell Dendritic Arbors And Glutamatergic Inputs After Injury In Vivo
Author Affiliations & Notes
  • Barbara J. Morquette
    Pathology and Cell biology,
    University de Montreal, Montreal, Quebec, Canada
  • Philippe P. Roux
    Institute for Research in Immunology and Cancer,
    University de Montreal, Montreal, Quebec, Canada
  • Elena Feinstein
    Research, Research, Quark pharmaceuticals inc., Ness Ziona, Israel
  • Anne R. McKinney
    Department of Pharmacology/Therapeutics, McGill University, Montreal, Quebec, Canada
  • Adriana Di Polo
    Pathology/Cell Biology, University of Montreal, Montreal, Quebec, Canada
  • Footnotes
    Commercial Relationships  Barbara J. Morquette, None; Philippe P. Roux, None; Elena Feinstein, Quark Pharmaceuticals inc. (E); Anne R. McKinney, None; Adriana Di Polo, None
  • Footnotes
    Support  CIHR (Canadian Institues of Health Research; FRSQ (Fond de Recherche en Santé du Québec)
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2689. doi:
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      Barbara J. Morquette, Philippe P. Roux, Elena Feinstein, Anne R. McKinney, Adriana Di Polo; mTOR Activity Restores Retinal Ganglion Cell Dendritic Arbors And Glutamatergic Inputs After Injury In Vivo. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2689.

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

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Purpose: : Dendrites are major determinants of how retinal neurons integrate and process incoming information. We previously showed that retinal ganglion cells (RGCs) undergo a significant reduction of dendritic arbors soon after axotomy, but the molecular mechanisms that underlie injury-induced dendritic remodeling are poorly understood. Here, we investigated the role of the mTOR (mammalian target of rapamycin) pathway in RGC dendritic structure and synaptic input after acute optic nerve lesion.

Methods: : Adult transgenic mice carrying the yellow fluorescent protein (YFP) gene were subjected to optic nerve axotomy. Retinal mTOR activity was manipulated by intraocular injection of siRNA against the mTOR repressor REDD2 (leading to mTOR stimulation), or by intraperitoneal administration of the mTOR inhibitor rapamycin. Retinal whole-mounts were prepared and YFP-positive RGC dendritic trees were reconstructed using Imaris software (Bitplane). mTOR activity in RGCs was examined by immunohistochemistry using an antibody against phospho-S6, a downstream target of mTOR. Excitatory synaptic inputs from bipolar cells onto RGC dendritic arbors were visualized using a Vglut-1 antibody.

Results: : Our data demonstrate that optic nerve axotomy leads to marked downregulation of mTOR activity in RGCs correlating with dendritic shrinkage at 3 days after injury (prior to RGC death onset). siREDD2 stimulated mTOR activity in injured RGCs and promoted an increase in total dendritic length, surface and complexity compared to retinas treated with control siRNA. Rapamycin blocked the effect of siREDD2 on dendritic growth and branching, confirming that this response occurred via mTOR stimulation. Importantly, increased mTOR activity in RGCs also restored glutamatergic bipolar cell inputs onto RGC dendritic shafts.

Conclusions: : Our study reveals a novel role for the mTOR pathway in the maintenance of RGC dendritic arbors and excitatory synaptic input after acute optic nerve lesion.

Keywords: ganglion cells 

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