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dc.contributor.author Cueva Vargas, Jorge L.
dc.contributor.author Osswald, Ingrid K.
dc.contributor.author Unsain, Nicolas
dc.contributor.author Aurousseau, Mark R.
dc.contributor.author Barker, Philip A.
dc.contributor.author Bowie, Derek
dc.contributor.author Di Polo, Adriana
dc.date.available 2019-02-05T18:27:26Z
dc.date.issued 2015-09
dc.identifier.citation Cueva Vargas, Jorge L.; Osswald, Ingrid K.; Unsain, Nicolas; Aurousseau, Mark R.; Barker, Philip A.; et al.; Soluble tumor necrosis factor alpha promotes retinal ganglion cell death in glaucoma via calcium-permeable ampa receptor activation; Society for Neuroscience; Journal of Neuroscience; 35; 35; 9-2015; 12088-12102
dc.identifier.issn 0270-6474
dc.identifier.uri http://hdl.handle.net/11336/69435
dc.description.abstract Loss of vision in glaucoma results from the selective death of retinal ganglion cells (RGCs). Tumor necrosis factorα (TNFα) signaling has been linked to RGC damage, however, the mechanism by which TNFα promotes neuronal death remains poorly defined. Using an in vivo rat glaucoma model, we show that TNFα is upregulated by Müller cells and microglia/macrophages soon after induction of ocular hypertension. Administration of XPro1595, a selective inhibitor of soluble TNFα, effectively protects RGC soma and axons. Using cobalt permeability assays, we further demonstrate that endogenous soluble TNFα triggers the upregulation of Ca2+-permeable AMPA receptor (CP-AMPAR) expression in RGCs of glaucomatous eyes. CP-AMPAR activation is not caused by defects in GluA2 subunit mRNA editing, but rather reflects selective downregulation of GluA2 in neurons exposed to elevated eye pressure. Intraocular administration of selective CP-AMPAR blockers promotes robust RGC survival supporting a critical role for non-NMDA glutamate receptors in neuronal death. Our study identifies glia-derived soluble TNFα as a major inducer of RGC death through activation of CP-AMPARs, thereby establishing a novel link between neuroinflammation and cell loss in glaucoma.
dc.format application/pdf
dc.language.iso eng
dc.publisher Society for Neuroscience
dc.rights info:eu-repo/semantics/openAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject AMPA RECEPTOR
dc.subject CALCIUM
dc.subject GLAUCOMA
dc.subject NEUROINFLAMMATION
dc.subject RETINAL GANGLION CELL
dc.subject TUMOR NECROSIS FACTOR
dc.subject.classification Otras Ciencias Biológicas
dc.subject.classification Ciencias Biológicas
dc.subject.classification CIENCIAS NATURALES Y EXACTAS
dc.title Soluble tumor necrosis factor alpha promotes retinal ganglion cell death in glaucoma via calcium-permeable ampa receptor activation
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2019-02-04T13:16:51Z
dc.journal.volume 35
dc.journal.number 35
dc.journal.pagination 12088-12102
dc.journal.pais Estados Unidos
dc.journal.ciudad Washington
dc.description.fil Fil: Cueva Vargas, Jorge L.. University of Montreal; Canadá
dc.description.fil Fil: Osswald, Ingrid K.. McGill University; Canadá
dc.description.fil Fil: Unsain, Nicolas. McGill University. Montreal Neurological Institute and Hospital; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina
dc.description.fil Fil: Aurousseau, Mark R.. McGill University; Canadá
dc.description.fil Fil: Barker, Philip A.. McGill University. Montreal Neurological Institute and Hospital; Canadá
dc.description.fil Fil: Bowie, Derek. McGill University; Canadá
dc.description.fil Fil: Di Polo, Adriana. University of Montreal; Canadá
dc.journal.title Journal of Neuroscience
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1523/JNEUROSCI.1273-15.2015
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/url/http://www.jneurosci.org/content/35/35/12088
dc.conicet.fuente individual


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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)