Evaluation of Chitosan/Aptamer Targeting TGF-β Receptor II Thermo-Sensitive Gel for Scarring in Rat Glaucoma Filtration Surgery.
OBJECTIVE
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.
Department of Ophthalmology Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
Xiaoyan
X
Zhu
Department of Ophthalmology Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
Duo
D
Xu
Department of Ophthalmology Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
Xiaomin
X
Zhu
Department of Molecular Biology Center, State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
Lei
L
Li
Department of Ophthalmology Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
Haijun
H
Li
Department of Ophthalmology Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
Feng
F
Guo
Department of Ophthalmology Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
Xia
X
Chen
Department of Molecular Biology Center, State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
Yan
Y
Tan
Department of Ophthalmology Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, People's Republic of China.
Lin
L
Xie
D000287:Administration, Topical; D000818:Animals; D052157:Aptamers, Nucleotide / Q000494:pharmacology; D001672:Biocompatible Materials / Q000494:pharmacology; D015153:Blotting, Western; D048271:Chitosan / Q000494:pharmacology*; D002921:Cicatrix / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D018463:Filtering Surgery; D005782:Gels; D005901:Glaucoma / Q000235:genetics / Q000378:metabolism / Q000601:surgery*; D020287:In Situ Nick-End Labeling; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics*; D014945:Wound Healing / Q000187:drug effects*
D052157:Aptamers, Nucleotide; D001672:Biocompatible Materials; D005782:Gels; D018125:Receptors, Transforming Growth Factor beta; D004247:DNA; D048271:Chitosan; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II