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@ARTICLE{Boccuni:283129,
      author       = {I. Boccuni and C. Bas-Orth and C. Bruehl and A. Draguhn and
                      R. Fairless$^*$},
      title        = {{G}lutamate transporter contribution to retinal ganglion
                      cell vulnerability in a rat model of multiple sclerosis.},
      journal      = {Neurobiology of disease},
      volume       = {187},
      issn         = {0969-9961},
      address      = {[Amsterdam]},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2023-01916},
      pages        = {106306},
      year         = {2023},
      note         = {#LA:B320#},
      abstract     = {Glial glutamate transporters actively participate in
                      neurotransmission and have a fundamental role in determining
                      the ambient glutamate concentration in the extracellular
                      space. Their expression is dynamically regulated in many
                      diseases, including experimental autoimmune
                      encephalomyelitis (EAE), a model of multiple sclerosis. In
                      EAE, a downregulation has been reported which may render
                      neurons more susceptible to glutamate excitotoxicity. In
                      this study, we have investigated the expression of GLAST
                      (EAAT1) and GLT-1 (EAAT2) in the retina of Brown Norway rats
                      following induction of myelin oligodendrocyte glycoprotein
                      (MOG)-EAE, which results in retinal ganglion cell (RGC)
                      degeneration and dysfunction. In addition, we tested whether
                      AAV-mediated overexpression of GLAST in the retina can
                      protect RGCs from degeneration. To address the impact of
                      glutamate transporter modulation on RGCs, we performed
                      whole-cell recordings and measured tonic NMDA
                      receptor-mediated currents in the absence and presence of a
                      glutamate-uptake blocker. We report that αOFF-RGCs show
                      larger tonic glutamate-induced currents than αON-RGCs, in
                      line with their greater vulnerability under
                      neuroinflammatory conditions. We further show that increased
                      AAV-mediated expression of GLAST in the retina does indeed
                      protect RGCs from degeneration during the inflammatory
                      disease. Collectively, our study highlights the
                      neuroprotective role of glutamate transporters in the EAE
                      retina and provides a characterization of tonic
                      glutamate-currents of αRGCs. The larger effects of
                      increased extracellular glutamate concentration on the
                      αOFF-subtype may underlie its enhanced vulnerability to
                      degeneration.},
      keywords     = {EAE (Other) / Glutamate (Other) / Glutamate transporters
                      (Other) / Neuroprotection (Other) / Optic neuritis (Other) /
                      Retinal ganglion cells (Other)},
      cin          = {B320 / HD01},
      ddc          = {570},
      cid          = {I:(DE-He78)B320-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37734623},
      doi          = {10.1016/j.nbd.2023.106306},
      url          = {https://inrepo02.dkfz.de/record/283129},
}