September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Anti-fibrotic effect of a multilayered nanoparticle system for delivery of siSPARC in a mouse model of experimental glaucoma surgery
Author Affiliations & Notes
  • Yang Fei Tan
    Nanyang Technological University, Singapore, Singapore
    Singapore Eye Research Institute, Singapore, Singapore
  • Li Fong Seet
    Singapore Eye Research Institute, Singapore, Singapore
  • Li Zhen Toh
    Singapore Eye Research Institute, Singapore, Singapore
  • Subbu Venkatraman
    Nanyang Technological University, Singapore, Singapore
  • Tina T Wong
    Singapore Eye Research Institute, Singapore, Singapore
    Nanyang Technological University, Singapore, Singapore
  • Footnotes
    Commercial Relationships   Yang Fei Tan, None; Li Fong Seet, None; Li Zhen Toh, None; Subbu Venkatraman, None; Tina Wong, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2930. doi:
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      Yang Fei Tan, Li Fong Seet, Li Zhen Toh, Subbu Venkatraman, Tina T Wong; Anti-fibrotic effect of a multilayered nanoparticle system for delivery of siSPARC in a mouse model of experimental glaucoma surgery. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2930.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Post-operative scarring following glaucoma filtration surgery is the major obstacle for any long-term surgical success. Therapeutic application of siRNAs is challenging due to sustainability of gene silencing and limits its potential effect. The secreted protein, acidic and rich in cysteine (SPARC) is a protein involved in extracellular matrix (ECM) production and organisation. The purpose of the study is to investigate the sustainability in siRNA silencing by using of a multilayered nanoparticle system for siSPARC in the prevention of fibrosis in a mouse model of conjunctival scarring.

Methods : Double SPARC siRNA layered layer by layer nanoparticles was fabricated with hydroxyapatite (HA) as the core and poly-L-arginine (ARG) as protective layers (HA|ARG|siRNA|ARG|siRNA|ARG). Modified glaucoma filtration surgeries were performed on 50 mice. At the end of each surgery, mice were injected with either siSPARC-loaded nanoparticles (n=50) or with nanoparticles loaded with scrambled siRNA (n=50). The mice were sacrificed on days 7 and 14, and the conjunctival tissues harvested. qPCR was performed on the tissues to quantify SPARC and collagen I expression. Western blot analysis was also performed on day 7.

Results : Knock down of SPARC was observed and maintained at 34.25% (P= 0.046) on Day 7 and 36.79% (P = 0.049) on Day 14. Collagen expression was reduced by 47.05% (P = 0.0031) on day 7 and 29.52% (P = 0.047) on Day 14. Both SPARC and collagen I protein expression was decreased on Day 7.

Conclusions : A multi-layered nanoparticle system provides prolonged siSPARC knock down and a reduction in postoperative fibrosis following experimental glaucoma surgery. Delivery of siRNA using a nanoparticles platform is a promising method for developing sustained siRNA therapeutics for treatment of fibrosis.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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