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dc.contributor.authorMurakami, Y.
dc.contributor.authorMatsumoto, Hidetaka
dc.contributor.authorRoh, Mi In
dc.contributor.authorSuzuki, J.
dc.contributor.authorHisatomi, T.
dc.contributor.authorIkeda, Y.
dc.contributor.authorMiller, Joan Whitten
dc.contributor.authorVavvas, Demetrios
dc.date.accessioned2014-10-21T17:14:44Z
dc.date.issued2012
dc.identifierQuick submit: 2013-09-06T03:08:09-04:00
dc.identifier.citationMurakami, Y., H. Matsumoto, M. Roh, J. Suzuki, T. Hisatomi, Y. Ikeda, J. W. Miller, and D. G. Vavvas. “Receptor Interacting Protein Kinase Mediates Necrotic Cone but Not Rod Cell Death in a Mouse Model of Inherited Degeneration.” Proceedings of the National Academy of Sciences 109 (36) (2012): 14598–14603.en_US
dc.identifier.issn1091-6490en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13065010
dc.description.abstractRetinitis pigmentosa comprises a group of inherited retinal photoreceptor degenerations that lead to progressive loss of vision. Although in most cases rods, but not cones, harbor the deleterious gene mutations, cones do die in this disease, usually after the main phase of rod cell loss. Rod photoreceptor death is characterized by apoptotic features. In contrast, the mechanisms and features of subsequent nonautonomous cone cell death remain largely unknown. In this study, we show that receptor-interacting protein (RIP) kinase mediates necrotic cone cell death in rd10 mice, a mouse model of retinitis pigmentosa caused by a mutation in a rod-specific gene. The expression of RIP3, a key regulator of programmed necrosis, was elevated in rd10 mouse retinas in the phase of cone but not rod degeneration. Although rd10 mice lacking Rip3 developed comparable rod degeneration to control rd10 mice, they displayed a significant preservation of cone cells. Ultrastructural analysis of rd10 mouse retinas revealed that a substantial fraction of dying cones exhibited necrotic morphology, which was rescued by Rip3 deficiency. Additionally, pharmacologic treatment with a RIP kinase inhibitor attenuated histological and functional deficits of cones in rd10 mice. Thus, necrotic mechanisms involving RIP kinase are crucial in cone cell death in inherited retinal degeneration, suggesting the RIP kinase pathway as a potential target to protect cone-mediated central and peripheral vision loss in patients with retinitis pigementosa.en_US
dc.language.isoen_USen_US
dc.publisherProceedings of the National Academy of Sciencesen_US
dc.relation.isversionofdoi:10.1073/pnas.1206937109en_US
dash.licenseLAA
dc.titleReceptor interacting protein kinase mediates necrotic cone but not rod cell death in a mouse model of inherited degenerationen_US
dc.typeJournal Articleen_US
dc.date.updated2013-09-06T07:08:43Z
dc.description.versionVersion of Recorden_US
dc.rights.holderYusuke Murakami, Hidetaka Matsumoto, Miin Roh, Jun Suzuki, Toshio Hisatomi, Yasuhiro Ikeda, Joan W Miller, and Demetrios G Vavvas
dc.relation.journalProceedings of the National Academy of Sciencesen_US
dash.depositing.authorVavvas, Demetrios
dc.date.available2014-10-21T17:14:44Z
dc.identifier.doi10.1073/pnas.1206937109*
workflow.legacycommentsPer new OSC interpretation can post pub.en_US
dash.contributor.affiliatedMatsumoto, Hidetaka
dash.contributor.affiliatedRoh, Mi In
dash.contributor.affiliatedMiller, Joan
dash.contributor.affiliatedVavvas, Demetrios


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