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标题：Deficiency in the metabolite receptor SUCNR1 (GPR91) leads to outer retinal lesions
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作者：Sandra Favret ; Francois Binet ; Eric Lapalme 等
期刊名称：Aging
出版年度：2013
卷号：5
期号：6
页码：427-444
出版社：U.S.Department of Health & Human Service
摘要：Age©\related. macular. degeneration. (AMD). is. a. prominent. cause. of. blindness. in. the.Western. world.. To.date,.itsmolecular.pathogenesis.as.well.as.the.sequence.of.events.leading.to.retinal. degeneration. remain.largely.ill©\defined..Whilethe. invasion. of. choroidal. neovasculature. in. the.retina. is. the. primary. mechanism. that. precipitates.loss. of.sight,.an.earlierdry.form.may. accompany. it.. Here.we. provide.the.first. evidence.for.the.protective. role. of.the. Retinal.Pigment.Epithelium(RPE)©\resident. metabolite.receptor,.succinate. receptor.1.(SUCNR1;. G©\Protein.coupled.Receptor©\91. (GPR91),. in.preventingdry. AMD©\like. lesions. of. the. outer. retina.. Genetic. analysis. of. 925. patients. with.geographic. atrophy.and. 1199. AMD©\freepeers.revealed.an.increased.risk.of.developing.geographic.atrophy.associated.with.intronic.variants.in.the.SUCNR1.gene..Inmice,.outer.retinal.expression.of.SUCNR1.is.observed.in.the.RPE.as.well.as.microglial.cells.and.decreases.progressively.withage.. Accordingly,. Sucnr1©\/©\. mice. show. signs. of. premature. sub©\retinal. dystrophy. with. accumulation. of. oxidized©\LDL,abnormal.thickening.of.Bruch's.membrane.and.a.buildup.of.subretinal.microglia.. The.accumulation.of.microglia.in.Sucnr1©\deficient.mice. is.likely.triggered.by.the.inefficient.clearance.of.oxidized.lipids.by.the.RPE.as.bone.marrow.transfer.of.wild©\type. microglia. into. Sucnr1©\/©\. mice. did. not. salvage. the. patho©\phenotype. and. systemic. lipolysis. was. equivalent. betweenwild©\type. and. control. mice.. Our. findings. suggest. that. deficiency. in. SUCNR1. is. a. possible. contributing. factor. to. thepathogenesis.of.dry.AMD.and.thus.broaden.our.understanding.of.this.clinically.unmet.need
关键词：AMD;.GPR91;.geographic.atrophy;.microglia;.succinate;.metabolite.receptor