April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
mTOR Activity Restores Retinal Ganglion Cell Dendritic Arbors After Axonal Injury in vivo
Author Affiliations & Notes
  • B. J. Morquette
    Pathology and Cell biology,
    University of Montreal, Montreal, Quebec, Canada
  • P. P. Roux
    Pathology and Cell Biology,
    University of Montreal, Montreal, Quebec, Canada
    Institute for Research in Immunology and Cancer, Montreal, Quebec, Canada
  • A. R. McKinney
    Department of Pharmacology/Therapeutics, McGill University, Montreal, Quebec, Canada
  • A. Di Polo
    Pathology and Cell Biology,
    University of Montreal, Montreal, Quebec, Canada
  • Footnotes
    Commercial Relationships  B.J. Morquette, None; P.P. Roux, None; A.R. McKinney, None; A. Di Polo, None.
  • Footnotes
    Support  Fond de Recherche en Santé du Québec (FRSQ).
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 4306. doi:
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      B. J. Morquette, P. P. Roux, A. R. McKinney, A. Di Polo; mTOR Activity Restores Retinal Ganglion Cell Dendritic Arbors After Axonal Injury in vivo. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4306.

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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 axonal injury. However, the molecular mechanisms that underlie injury-induced dendritic remodeling are poorly defined. Here, we investigated the role of the mTOR (mammalian target of rapamycin) pathway in RGC dendritic structure after acute optic nerve lesion.

Methods: : Adult transgenic mice carrying the yellow fluorescent protein (YFP) gene under control of the Thy-1 promoter, which allows visualization of RGC dendrites, were subjected to optic nerve axotomy. Retinal mTOR activity was manipulated using two approaches: i) intraocular injection of siRNA against the mTOR repressor REDD2, therefore increasing mTOR activity; and ii) intraperitoneal administration of rapamycin, an mTOR inhibitor. Three days after lesion, prior to the onset of RGC death, retinal whole-mounts were prepared and YFP-positive RGC dendritic trees were reconstructed from images obtained by confocal microscopy using Imaris software (Bitplane). mTOR activity in RGCs was examined by immunohistochemistry using an antibody against phospho-S6, a downstream target of mTOR.

Results: : Our data demonstrate that optic nerve axotomy leads to marked downregulation of mTOR activity in RGCs, which correlated with dendritic shrinkage at 3 days after injury. Treatment with siREDD2 stimulated mTOR activity in axotomized RGCs and promoted a significant increase in total dendritic length and surface (n=10) compared to retinas treated with control siRNA (n=10). Scholl analysis revealed a marked increase in the complexity of dendritic arbors from RGCs with increased mTOR activity. Administration of rapamycin completely blocked the effect of siREDD2 on dendritic growth and branching confirming that this response occurred via mTOR stimulation.

Conclusions: : Our study reveals a novel role for the mTOR pathway in the maintenance of dendritic structure in adult, injured RGCs.

Keywords: ganglion cells • neuroprotection • regeneration 

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