dc.contributor.author | Farrar, Gwyneth | |
dc.contributor.author | Campbell, Matthew | |
dc.contributor.author | Humphries, Peter | |
dc.contributor.author | Humphries, Marian | |
dc.date.accessioned | 2023-05-23T14:48:59Z | |
dc.date.available | 2023-05-23T14:48:59Z | |
dc.date.issued | 2021 | |
dc.date.submitted | 2021 | en |
dc.identifier.citation | Cassidy PS, Kelly RA, Reina-Torres E, Sherwood JM, Humphries MM, Kiang AS, Farrar GJ, O'Brien C, Campbell M, Stamer WD, Overby DR, Humphries P, O'Callaghan J. siRNA targeting Schlemm's canal endothelial tight junctions enhances outflow facility and reduces IOP in a steroid-induced OHT rodent model, Molecular Therapy - Methods and Clinical Development, 2020 Oct 31;20:86-94 | en |
dc.identifier.other | Y | |
dc.description.abstract | Systemic or localized application of glucocorticoids (GCs) can
lead to iatrogenic ocular hypertension, which is a leading
cause of secondary open-angle glaucoma and visual impair ment. Previous work has shown that dexamethasone increases
zonula occludens-1 (ZO-1) protein expression in trabecular
meshwork (TM) cells, and that an antisense oligonucleotide
inhibitor of ZO-1 can abolish the dexamethasone-induced in crease in trans-endothelial flow resistance in cultured
Schlemm’s canal (SC) endothelial and TM cells. We have pre viously shown that intracameral inoculation of small inter fering RNA (siRNA) targeting SC endothelial cell tight junc tion components, ZO-1 and tricellulin, increases aqueous
humor outflow facility ex vivo in normotensive mice by
reversibly opening SC endothelial paracellular pores. In this
study, we show that targeted siRNA downregulation of these
SC endothelial tight junctions reduces intraocular pressure
(IOP) in vivo, with a concomitant increase in conventional
outflow facility in a well-characterized chronic steroid induced mouse model of ocular hypertension, thus represent ing a potential focused clinical application for this therapy in
a sight-threatening scenario. | en |
dc.format.extent | 86-94 | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | Molecular Therapy - Methods and Clinical Development; | |
dc.relation.ispartofseries | 20; | |
dc.rights | Y | en |
dc.subject | glucocorticoids (GCs) | en |
dc.subject | intraocular pressure; | en |
dc.subject | Schlemm's canal | en |
dc.subject | Trabecular meshwork | en |
dc.subject | Tight junctions | en |
dc.subject | Primary open angle glaucoma | en |
dc.subject | Pores | en |
dc.subject | Outflow facility | en |
dc.subject | Ocular hypertension | en |
dc.subject | Intracameral | en |
dc.subject | Schlemm’s canal | en |
dc.title | siRNA targeting Schlemm's canal endothelial tight junctions enhances outflow facility and reduces IOP in a steroid-induced OHT rodent model | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/gjfarrar | |
dc.identifier.peoplefinderurl | http://people.tcd.ie/campbem2 | |
dc.identifier.peoplefinderurl | http://people.tcd.ie/phumphrs | |
dc.identifier.peoplefinderurl | http://people.tcd.ie/mhumphri | |
dc.identifier.rssinternalid | 239070 | |
dc.identifier.doi | http://dx.doi.org/10.1016/j.omtm.2020.10.022 | |
dc.rights.ecaccessrights | openAccess | |
dc.contributor.sponsor | Science Foundation Ireland | en |
dc.contributor.sponsorGrantNumber | 16/IA/4452 | en |
dc.identifier.uri | http://hdl.handle.net/2262/102711 | |