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Title: Targeted therapy for the post-operative conjunctiva : SPARC silencing reduces collagen deposition
Authors: Seet, Li Fong
Tan, Yang Fei
Toh, Li Zhen
Chu, Stephanie Wai Ling
Lee, Ying Shi
Venkatraman, Subbu Subramanian
Wong, Tina Tzee Ling
Keywords: Engineering::Materials
Issue Date: 2018
Source: Seet, L. F., Tan, Y. F., Toh, L. Z., Chu, S. W. L., 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. doi:10.1136/bjophthalmol-2018-311937
Journal: British Journal of Ophthalmology
Abstract: Background: 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.
ISSN: 0007-1161
DOI: 10.1136/bjophthalmol-2018-311937
Rights: © 2018 The Author(s) (or their employer(s)). Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an Open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:
Fulltext Permission: open
Fulltext Availability: With Fulltext
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