PT - JOURNAL ARTICLE AU - Frédéric Lebrun-Julien AU - Laure Duplan AU - Vincent Pernet AU - Ingrid Osswald AU - Przemyslaw Sapieha AU - Philippe Bourgeois AU - Kathleen Dickson AU - Derek Bowie AU - Philip A. Barker AU - Adriana Di Polo TI - Excitotoxic Death of Retinal Neurons <em>In Vivo</em> Occurs via a Non-Cell-Autonomous Mechanism AID - 10.1523/JNEUROSCI.0831-09.2009 DP - 2009 Apr 29 TA - The Journal of Neuroscience PG - 5536--5545 VI - 29 IP - 17 4099 - http://www.jneurosci.org/content/29/17/5536.short 4100 - http://www.jneurosci.org/content/29/17/5536.full SO - J. Neurosci.2009 Apr 29; 29 AB - The central hypothesis of excitotoxicity is that excessive stimulation of neuronal NMDA-sensitive glutamate receptors is harmful to neurons and contributes to a variety of neurological disorders. Glial cells have been proposed to participate in excitotoxic neuronal loss, but their precise role is defined poorly. In this in vivo study, we show that NMDA induces profound nuclear factor κB (NF-κB) activation in Müller glia but not in retinal neurons. Intriguingly, NMDA-induced death of retinal neurons is effectively blocked by inhibitors of NF-κB activity. We demonstrate that tumor necrosis factor α (TNFα) protein produced in Müller glial cells via an NMDA-induced NF-κB-dependent pathway plays a crucial role in excitotoxic loss of retinal neurons. This cell loss occurs mainly through a TNFα-dependent increase in Ca2+-permeable AMPA receptors on susceptible neurons. Thus, our data reveal a novel non-cell-autonomous mechanism by which glial cells can profoundly exacerbate neuronal death following excitotoxic injury.