Evaluation of Chitosan/Aptamer Targeting TGF-β Receptor II Thermo-Sensitive Gel for Scarring in Rat Glaucoma Filtration Surgery

Invest Ophthalmol Vis Sci. 2015 Aug;56(9):5465-76. doi: 10.1167/iovs.15-16683.

Abstract

Purpose: This study was designed to develop a chitosan (CS) thermo-sensitive gel combined with aptamer S58 targeting transforming growth factor-beta receptor II (TGF-β RII) and to investigate the antifibrotic effects of CS/S58 gel in a rat glaucoma filtration surgery (GFS) model.

Methods: In vitro aptamer S58 release rate from the CS/S58 gel were detected, and the effect of mitomycin-C (MMC), TGF-β2, CS, or CS/S58 gel on wound healing were investigated in a rat GFS model by detecting scar-related factors and the involved inflammatory response. The levels of collagen I and α-smooth muscle actin (α-SMA) were detected by immunohistochemistry and Western blotting.

Results: The control and TGF-β2 eyes exhibited densely packed collagen fibers with no evidence of filtration after day 7. The pronounced increase in filtration efficiency was associated with thinner fibers, and a loosely organized subconjunctival matrix was observed in CS/S58 gel-treated eyes. The levels of collagen I and α-SMA were downregulated in CS/S58 gel-treated eyes. Conjunctival fibroblast proliferation and the inflammation response were also suppressed in the CS/S58 gel-treated group.

Conclusions: This study presents evidence that the antifibrotic effect of chitosan in combination with aptamer S58 is superior to chitosan alone in a rat GFS model. Chitosan/S58 gel may be considered to be a promising antifibrotic agent for a local drug therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Aptamers, Nucleotide / pharmacology
  • Biocompatible Materials / pharmacology
  • Blotting, Western
  • Chitosan / pharmacology*
  • Cicatrix / genetics*
  • Cicatrix / pathology
  • Cicatrix / prevention & control
  • Conjunctiva / drug effects
  • Conjunctiva / metabolism
  • Conjunctiva / pathology
  • DNA / genetics
  • Disease Models, Animal
  • Down-Regulation / drug effects*
  • Filtering Surgery*
  • Gels
  • Glaucoma / genetics
  • Glaucoma / metabolism
  • Glaucoma / surgery*
  • In Situ Nick-End Labeling
  • Male
  • Protein Serine-Threonine Kinases / biosynthesis
  • Protein Serine-Threonine Kinases / genetics*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / biosynthesis
  • Receptors, Transforming Growth Factor beta / genetics*
  • Wound Healing / drug effects*

Substances

  • Aptamers, Nucleotide
  • Biocompatible Materials
  • Gels
  • Receptors, Transforming Growth Factor beta
  • DNA
  • Chitosan
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II