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dc.contributor.author
Cueva Vargas, Jorge L.
dc.contributor.author
Osswald, Ingrid K.
dc.contributor.author
Unsain, Nicolas
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Aurousseau, Mark R.
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Barker, Philip A.
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Bowie, Derek
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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
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Calcium
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Glaucoma
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Neuroinflammation
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Retinal Ganglion Cell
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Tumor Necrosis Factor
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Otras Ciencias Biológicas
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Ciencias Biológicas
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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


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