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Apolipoprotein E4 impairs the response of neurodegenerative retinal microglia and prevents neuronal loss in glaucoma

dc.rights.licenseopenen_US
dc.contributor.authorMARGETA, Milica
dc.contributor.authorYIN, Zhuoran
hal.structure.identifierNutrition et Neurobiologie intégrée [NutriNeuro]
dc.contributor.authorMADORE, Charlotte
dc.contributor.authorPITTS, Kristen
dc.contributor.authorLETCHER, Sophia
dc.contributor.authorTANG, Jing
dc.contributor.authorJIANG, Shuhong
dc.contributor.authorGAUTHIER, Christian
dc.contributor.authorSILVEIRA, Sebastian
dc.contributor.authorSCHROEDER, Caitlin
dc.contributor.authorLAD, Eleonora
dc.contributor.authorPROIA, Alan
dc.contributor.authorTANZI, Rudolph
dc.contributor.authorHOLTZMAN, David
dc.contributor.authorKRASEMANN, Susanne
dc.contributor.authorCHEN, Dong Feng
dc.contributor.authorBUTOVSKY, Oleg
dc.date.accessioned2022-12-19T12:42:08Z
dc.date.available2022-12-19T12:42:08Z
dc.date.issued2022-09-13
dc.identifier.issn1097-4180en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/171579
dc.description.abstractEnThe apolipoprotein E4 (APOE4) allele is associated with an increased risk of Alzheimer disease and a decreased risk of glaucoma, but the underlying mechanisms remain poorly understood. Here, we found that in two mouse glaucoma models, microglia transitioned to a neurodegenerative phenotype characterized by upregulation of Apoe and Lgals3 (Galectin-3), which were also upregulated in human glaucomatous retinas. Mice with targeted deletion of Apoe in microglia or carrying the human APOE4 allele were protected from retinal ganglion cell (RGC) loss, despite elevated intraocular pressure (IOP). Similarly to Apoe-/- retinal microglia, APOE4-expressing microglia did not upregulate neurodegeneration-associated genes, including Lgals3, following IOP elevation. Genetic and pharmacologic targeting of Galectin-3 ameliorated RGC degeneration, and Galectin-3 expression was attenuated in human APOE4 glaucoma samples. These results demonstrate that impaired activation of APOE4 microglia is protective in glaucoma and that the APOE-Galectin-3 signaling can be targeted to treat this blinding disease. Copyright © 2022 Elsevier Inc. All rights reserved.
dc.language.isoENen_US
dc.subject.enMicroglia
dc.subject.enAPOE4
dc.subject.enNeurodegeneration
dc.subject.enRetina
dc.subject.enGlaucoma
dc.subject.enAlzheimer disease
dc.subject.enLgals3
dc.subject.enGalectin-3
dc.subject.enneuroprotection
dc.title.enApolipoprotein E4 impairs the response of neurodegenerative retinal microglia and prevents neuronal loss in glaucoma
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.immuni.2022.07.014en_US
dc.subject.halSciences du Vivant [q-bio]/Neurosciences [q-bio.NC]en_US
dc.identifier.pubmed35977543en_US
bordeaux.journalImmunityen_US
bordeaux.page1627-1644en_US
bordeaux.volume55en_US
bordeaux.hal.laboratoriesNutriNeurO (Laboratoire de Nutrition et Neurobiologie Intégrée) - UMR 1286en_US
bordeaux.issue9en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINRAEen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-03906354
hal.version1
hal.date.transferred2022-12-19T12:42:32Z
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
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