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Sam Young Yoon, Hungwon Tchah, Myoung Joon Kim, Jae Yong Kim; The effect of sirolimus and tacrolimus for modification of conjunctival wound healing response. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2757.
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To evaluate the effect of sirolimus and tacrolimus for modification of conjunctival wound healing response in vitro and in vivo.
Study 1. Human Tenon’s fibroblast (HTF) was subcultured at culture media. Serum starvation of HTF was done for 24 hours, then sirolimus and tacrolimus were treated. One hour later, PDGF (platelet-derived growth factor) or TGF-β (transforming growth factor beta)1 was injected at HTF. Proliferation, transdifferentiation and migration of HTF were observed. Study 2. Twenty rabbits were involved, then divided equally into 5 groups. Incision was made at superior fornix and normal saline (group A), mitomycin-C (group B), sirolimus (group C), tacrolimus (group D) and 10% ethanol (group E)-coated silicone plate was inserted at subtenon space in each groups. Digital photographs of the conjunctiva around silicone plate were taken to evaluate conjunctival congestion at postoperative 1 week and 4 weeks. At postoperative 4 weeks, it was obtained that conjunctival and tenon tissue around silicone plate, then inflammatory cell, fibroblast, myofibroblast, blood vessel and goblet cell were counted.
Study 1. Proliferation, transdifferentiation and migration of HTF were suppressed by sirolimus and tacrolimus in vitro. Study 2. Conjunctival congestion was significantly reduced at postoperative 4 weeks than that at 1 week in all groups (P<0.05). Conjunctiva was significantly less congested in the group inserted tacrolimus-coated silicone plate than that in other groups at postoperative 1 week and 4 weeks (P<0.05). Corneal paracentral opacity was observed at 1 eye in mitomycin group. Severe inflammation and silicone plate loss were occurred at 1 eye in 10% ethanol group. In mitomycin group, abundant inflammatory cells and fibroblasts were observed and the number of goblet cell was lowest among all groups. In tacrolimus group, however, the number of inflammatory cell and fibroblast was the least among all groups and goblet cells were not decreased comparing with other control groups.
Sirolimus and tacrolimus suppressed the proliferation, transdifferentiation and migration of HTF by PDGF and TGF-β1 in vitro. In rabbit model, sirolimus and tacrolimus also inhibit inflammatory reaction and fibrosis except adverse effect. Therefore sirolimus and tacrolimus may be considered as an alternative of mitomycin C which frequently used in glaucoma and pterygium surgery.
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