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.
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http://dx.doi.org/10.1167/iovs.15-16683 | DOI Listing |
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