Targeted therapy for the post-operative conjunctiva: SPARC silencing reduces collagen deposition

The British Journal of Ophthalmology
Li Fong SeetTina T Wong

Abstract

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. 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 (...Continue Reading

References

Dec 1, 1996·Kidney International·R H PichlerW G Couser
Apr 5, 2000·The Journal of Clinical Investigation·A M DelanyE Canalis
Dec 5, 2000·Matrix Biology : Journal of the International Society for Matrix Biology·R A Brekken, E H Sage
Dec 18, 2001·Arteriosclerosis, Thrombosis, and Vascular Biology·C R DhoreM J Daemen
Sep 17, 2002·Current Opinion in Cell Biology·Paul Bornstein, E Helene Sage
Mar 27, 2007·Journal of Dental Research·N MartinekM Ringuette
May 25, 2007·The Journal of Biological Chemistry·Tyler J RentzAmy D Bradshaw
Oct 16, 2007·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Arno HueberPeter J Esser
Oct 3, 2009·Journal of Cell Communication and Signaling·Amy D Bradshaw
Nov 11, 2009·Acta Ophthalmologica·Dimitris PapaconstantinouGerasimos Georgopoulos
Feb 22, 2012·Clinical & Experimental Ophthalmology·William H Morgan, Dao-Yi Yu
Jul 18, 2012·The Open Rheumatology Journal·Jessica Trombetta-Esilva, Amy D Bradshaw
Mar 8, 2016·Journal of Glaucoma·Joseph F PanarelliPaul A Sidoti
Jan 26, 2017·Investigative Ophthalmology & Visual Science·Henrietta HoLi-Fong Seet

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Citations

Jul 28, 2020·Acta Ophthalmologica·Rachel S ChongTina T Wong
Jan 8, 2021·Veterinary Ophthalmology·András M KomáromyShin Ae Park
Aug 29, 2021·Pharmaceutics·Yolanda Diebold, Laura García-Posadas

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Methods Mentioned

BETA
PCR
flow cytometry
confocal microscopy

Software Mentioned

AS
Guava Nexin
OCT
Image Studio Lite
siSparc
SPSS

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