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dc.contributor.authorHUMPHRIES, MARIANen
dc.contributor.authorHUMPHRIES, PETERen
dc.contributor.authorCAMPBELL, MATTHEWen
dc.contributor.authorFARRAR, JANEen
dc.contributor.authorKENNA, PAULen
dc.contributor.authorGOBBO, OLIVIEROen
dc.date.accessioned2013-07-08T11:51:09Z
dc.date.available2013-07-08T11:51:09Z
dc.date.issued2011en
dc.date.submitted2011en
dc.identifier.citationCampbell M, Humphries MM, Nguyen ATH, Gobbo OL, Tam LCS, Suzuki M, Hanrahan F, Ozaki E, Farrar G-J, Kiang A-S, Kenna PF, Humphries P., Systemic low-molecular weight drug delivery to pre-selected neuronal regions, EMBO Molecular Medicine, 3, 4, 2011, 235?245en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/66642
dc.descriptionPUBLISHEDen
dc.description.abstractWe describe a procedure for controlled, periodic, reversible modulation of selected regions of the blood-brain barrier (BBB) or the inner-blood-retina barrier (iBRB) based on incorporation into an AAV-2/9 vector of a doxycycline-inducible gene encoding shRNA targeting claudin-5, one of 30 or so proteins constituting the BBB and iBRB. The vector may be introduced stereotaxically into pre-selected regions of the brain or into the retina, rendering these regions permeable to low-molecular weight compounds up to approximately 1kDa for the period of time during which the inducing agent, doxycycline, is administered in drinking water, but excluding potentially toxic higher molecular weight materials. We report on the use of barrier modulation in tandem with systemic drug therapy to prevent retinal degeneration and to suppress laser-induced choroidal neovascularization (CNV), the latter being the hallmark pathology associated with the exudative, or wet, form of age-related macular degeneration (AMD). These observations constitute the basis of a minimally invasive systemic therapeutic modality for retinal diseases, including retinitis pigmentosa and AMD, where, in early stage disease, the iBRB is intact and impervious to systemically administered drugs. ? 2011 EMBO Molecular Medicine.en
dc.description.sponsorshipThe Ocular Genetics Unit at TCD is supported by Science Foundation Ireland (SFI), The Wellcome Trust, Irish Research Council for Science Engineering and Technology (IRCSET) and Fighting Blindness Ireland (FB-Ireland). Health Research Board of Ireland (HRB), Enterprise Ireland (EI) and the US Depart- ment of Defense-Telemedicine and Advanced Technology Research Center (TATRC). We would like to thank Caroline Woods, Charles Murray, David Flynn and Rebecca Robertson for animal breeding and husbandry. The authors would also like to thank Dr Christian Kerskens for his advice with MRI experiments and the Research Foundation at the Royal Victoria Eye and Ear Hospital for assistance in the acquisition of the Iridex laser system.en
dc.format.extent235-245en
dc.language.isoenen
dc.relation.ispartofseriesEMBO Molecular Medicineen
dc.relation.ispartofseries3en
dc.relation.ispartofseries4en
dc.rightsYen
dc.subjectadenovirus vector; claudin 5; doxycycline; drinking water; enhanced green fluorescent protein; gadolinium pentetate; short hairpin RNAen
dc.subject.lcshadenovirus vector; claudin 5; doxycycline; drinking water; enhanced green fluorescent protein; gadolinium pentetate; short hairpin RNAen
dc.titleSystemic low-molecular weight drug delivery to pre-selected neuronal regionsen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/mhumphrien
dc.identifier.peoplefinderurlhttp://people.tcd.ie/campbem2en
dc.identifier.peoplefinderurlhttp://people.tcd.ie/gjfarraren
dc.identifier.peoplefinderurlhttp://people.tcd.ie/phumphrsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/ogobboen
dc.identifier.rssinternalid78984en
dc.subject.TCDThemeGenes & Societyen
dc.identifier.rssurihttp://dx.doi.org/10.1002/emmm.201100126en


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