Please use this identifier to cite or link to this item: https://doi.org/10.1136/bjophthalmol-2018-311937
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dc.titleTargeted therapy for the post-operative conjunctiva: SPARC silencing reduces collagen deposition
dc.contributor.authorSeet L.F.
dc.contributor.authorTan Y.F.
dc.contributor.authorToh L.Z.
dc.contributor.authorChu S.W.
dc.contributor.authorLee Y.S.
dc.contributor.authorVenkatraman S.S.
dc.contributor.authorWong T.T.
dc.date.accessioned2019-02-20T01:22:13Z
dc.date.available2019-02-20T01:22:13Z
dc.date.issued2018
dc.identifier.citationSeet L.F., Tan Y.F., Toh L.Z., Chu S.W., Lee Y.S., Venkatraman S.S., Wong T.T. (2018). Targeted therapy for the post-operative conjunctiva: SPARC silencing reduces collagen deposition. British Journal of Ophthalmology 102 (10) : 1460-1470. ScholarBank@NUS Repository. https://doi.org/10.1136/bjophthalmol-2018-311937
dc.identifier.issn71161
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/151600
dc.description.abstractBackground To develop targeted antifibrotic therapy for glaucoma filtration surgery; this study determines the effectiveness of small interfering RNA (siRNA) to reduce in vivo secreted protein acidic and rich in cysteine (SPARC) expression using the mouse model of conjunctival scarring. Methods Experimental surgery was performed as described for the mouse model of conjunctival scarring. Scrambled (siScram) or Sparc (siSparc) siRNAs, loaded on layer-by-layer (LbL) nanoparticles, were injected into the conjunctiva immediately after surgery. Expression of Sparc, Col1a1, Fn1 and Mmp14 was measured by real-Time PCR and immunoblotting on days 7 and 14 postsurgery. Live imaging of the operated eyes was performed using slit lamp, anterior segment-optical coherence tomography and confocal microscopy. Tissue pathology was evaluated by histochemical and immunofluorescent analyses of operated conjunctival cryosections. Tissue apoptosis was quantitated by annexin V assay. Results siSparc, delivered via expanded LbL nanoparticles, significantly inhibited Sparc transcription in both day 7 (2.04-fold) and day 14 (1.39-fold) treated tissues. Sparc suppression on day 7 was associated with a significant reduction of Col1a1 (2.52-fold), Fn1 (2.89-fold) and Mmp14 (2.23-fold) mRNAs. At the protein level, both SPARC and collagen 1A1 (COL1A1) were significantly reduced at both time points with siSparc treatment. Nanoparticles were visualised within cell-like structures by confocal microscopy, while overt tissue response or apoptosis was not observed. Conclusions SPARC targeted therapy effectively reduced both SPARC and collagen production in the operated mouse conjunctiva. This proof-of-concept study suggests that targeted treatment of fibrosis in glaucoma surgery is safe and feasible, with the potential to extend to a range of potential genes associated with fibrosis. © Author(s) (or their employer(s)) 2018.
dc.publisherBMJ Publishing Group
dc.sourceScopus
dc.subjectConjunctiva
dc.subjectExperimental-Animal models
dc.subjectTreatment surgery
dc.subjectWound healing
dc.typeArticle
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1136/bjophthalmol-2018-311937
dc.description.sourcetitleBritish Journal of Ophthalmology
dc.description.volume102
dc.description.issue10
dc.description.page1460-1470
dc.published.statePublished
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