Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/74446
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dc.contributorSchool of Optometry-
dc.creatorWang, K-
dc.creatorPeng, B-
dc.creatorXiao, J-
dc.creatorWeinreb, O-
dc.creatorYoudim, MBH-
dc.creatorLin, B-
dc.date.accessioned2018-03-29T07:16:50Z-
dc.date.available2018-03-29T07:16:50Z-
dc.identifier.issn0146-0404-
dc.identifier.urihttp://hdl.handle.net/10397/74446-
dc.language.isoenen_US
dc.publisherAssociation for Research in Vision and Ophthalmologyen_US
dc.rightsCopyright 2017 The Authorsen_US
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NonDerivatives 4.0 International License.en_US
dc.subjectIron-chelating drugsen_US
dc.subjectMicrogliaen_US
dc.subjectPhotoreceptorsen_US
dc.subjectRd10 miceen_US
dc.subjectVision rescueen_US
dc.titleIron-chelating drugs enhance cone photoreceptor survival in a mouse model of retinitis pigmentosaen_US
dc.typeJournal/Magazine Articleen_US
dc.identifier.spage5287-
dc.identifier.epage5297-
dc.identifier.volume58-
dc.identifier.issue12-
dc.identifier.doi10.1167/iovs.17-22096-
dcterms.abstractPURPOSE. Retinitis pigmentosa (RP) is a group of hereditary retinal degeneration in which mutations commonly result in the initial phase of rod cell death followed by gradual cone cell death. The mechanisms by which the mutations lead to photoreceptor cell death in RP have not been clearly elucidated. There is currently no effective treatment for RP. The purpose of this work was to explore iron chelation therapy for improving cone survival and function in the rd10 mouse model of RP. METHODS. Two iron-chelating drugs, 5-(4-(2-hydroxyethyl) piperazin-1-yl (methyl)-8-hydroxyquinoline (VK28) and its chimeric derivative 5-(N-methyl-N-propargyaminomethyl)-quinoline- 8-oldihydrochloride (VAR10303), were injected intraperitoneally to rd10 mice every other day starting from postnatal day 14. We investigate the effects of the two compounds on cone rescue at three time points, using a combination of immunocytochemistry, RT-PCR, Western blot analysis, and a series of visual function tests. RESULTS. VK28 and VAR10303 treatments partially rescued cones, and significantly improved visual function in rd10 mice. Moreover, we showed that the neuroprotective effects of VK28 and VAR10303 were correlated to inhibition of neuroinflammation, oxidative stress, and apoptosis. Furthermore, we demonstrated that downregulation of NF-kB and p53 is likely to be the mechanisms by which proinflammatory mediators and apoptosis are reduced in the rd10 retina, respectively. CONCLUSIONS. VK28 and VAR10303 provided partial histologic and functional rescue of cones in RD10 mice. Our study demonstrated that iron chelation therapy might represent an effective therapeutic strategy for RP patients.-
dcterms.accessRightsopen accessen_US
dcterms.bibliographicCitationInvestigative ophthalmology and visual science, 2017, v. 58, no. 12, p. 5287-5297-
dcterms.isPartOfInvestigative ophthalmology and visual science-
dcterms.issued2017-
dc.identifier.scopus2-s2.0-85032151845-
dc.identifier.eissn1552-5783-
dc.identifier.rosgroupid2017006199-
dc.description.ros2017-2018 > Academic research: refereed > Publication in refereed journal-
dc.description.validate201802 bcrc-
dc.description.oaVersion of Recorden_US
dc.identifier.FolderNumberOA_IR/PIRAen_US
dc.description.pubStatusPublisheden_US
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