AIM: To investigate the effect of luteolin on tissue fibrosis in the filtering area following glaucoma trabeculectomy, and its relationship with the Wnt3a/β-catenin signaling pathway.METHODS: Rabbits were selected to establish a fibrosis model after glaucoma trabeculectomy, and randomly divided into the sham operation group, model group, luteolin-L group and luteolin-H group. Dynamic monitoring of postoperative intraocular pressure was performed in all groups. Slit-lamp biomicroscopy was used to observe postoperative conjunctival morphological changes, conjunctival healing degree, corneal integrity, and anterior chamber inflammatory responses in the filtering bleb area. HE staining was performed to evaluate conjunctival epithelial integrity, subepithelial fibrous proliferation, and inflammatory cell infiltration in the filtering tissues. Masson's trichrome staining was applied to assess collagen deposition and the degree of tissue fibrosis. The expression of α-SMA was observed by immunohistochemical staining. The mRNA and protein expression levels of Wnt3a, Wnt7a, Wnt2b, β-catenin, LC3-I, LC3-II and p62-SQSTM1 in conjunctival tissues of the operative area were quantitatively detected by RT-qPCR and Western blot, respectively.RESULTS:Postoperative dynamic monitoring showed that the luteolin-H group achieved significantly better intraocular pressure control than the luteolin-L group compared with the model group(all P<0.05). Slit lamp observations confirmed that luteolin effectively ameliorated postoperative conjunctival injury, alleviated anterior chamber inflammatory response, and maintained the structural stability of the filtering area. HE and Masson staining revealed that luteolin intervention reduced conjunctival epithelial damage and inflammatory cell infiltration, markedly inhibited fibroblast proliferation, neovascularization and excessive collagen deposition, and significantly delayed the progression of filtering bleb scarring, with stronger effects in the luteolin-H group than luteolin-L group compared with the model group. Immunohistochemical staining demonstrated that luteolin intervention decreased the positive expression rate of α-SMA. Molecular assays indicated that the luteolin-H group had lower expression levels of Wnt3a, β-catenin and LC3-II/LC3-I, and the highest p62-SQSTM1 level in the operative site relative to the model group and luteolin-L group(all PSymbol|@@0.05). No significant intergroup differences were observed in Wnt2b and Wnt7a expression. These findings suggested that luteolin could specifically regulated the Wnt3a pathway and dose-dependently suppressed the activation of the Wnt3a/β-catenin pathway after glaucoma trabeculectomy, downregulated LC3-II/LC3-I expression, upregulated p62-SQSTM1 levels, and inhibited excessive autophagy activation.CONCLUSION: Luteolin can significantly inhibit filtering bleb fibrosis after trabeculectomy, which may reduce the degree of fibrosis via the Wnt3a/β-catenin pathway.

Background Clinical study showed that FP-7/FP-8 Ahmed glaucoma valve implantation is effective and safe for the adult refractory glaucoma.However,it is welt-known that childhood glaucomatous eyes have different pathogenesis and protean clinical manifestations.So the efficacy of FP-7/FP-8 Ahmed glaucoma valve implantation in child deserves some attention.Objective This study was to retrospectively evaluate the efficacy and safety of FP-7/FP-8 Ahmed glaucoma valve implantation for refractory glaucoma in children.Methods The clinical data of 30 eyes of 26 children with refractory glaucoma who undergone FP-7/FP-8 Ahmed glaucoma valve implantation in the Center Hospital of Cangzhou from October 2008 to April 2011 were retrospectively analyzed.The age of patients was 4 months to 16.5 years.The patients included ocular hypertension after trabculectomy/goniotomy for cogenital glaucoma,later stage of cogenital glaucoma,aphakic or pseudophakic glaucoma,traumatic glaucoma and Sturge-Weber syndrome.The follow-up ranged from 1 week to 24 months to obverse the changes of intraocular pressure (IOP),postoperative complications and cumulative success rate.Results The mean IOP was significantly different among various time points (F=58.929,P＜0.05).The IOP was (36.93± 10.56) mmHg in preoperation and (13.13± 3.34),(14.13±3.15),(15.93±4.76),(17.96±5.37),(19.74±5.43) mmHg 1 week,1 month,6 months,12 months,24 months following surgery,showing significant reduce after operation.Compared with preoperative IOP,the IOP of 1 week,1 month,6,12,24 months after AGI was significant decreased,with significant differences between them (t =11.641,11.458,10.688,7.988,8.018,all at P ＜ 0.05).The total cumulative success rate after Ahmed glaucoma valve implant was 100％,96.67％,93.21％,85.76％ and 71.46％ 1 week,1 month,6 months,12 months,24 months after surgery.The postoperative complications occurred in 8 eyes,including shallow anterior chamber,drainage tube obstruction,hyphema of anterior chamber and valve exposure,and these were cured by medicine and surgery.No serious complication appeared in all patients after operation.Conclusions FP-7/FP-8 Ahmed glaucoma valve implantation is an effective and safe method for the treatment of refractory glaucoma,and it can be considered as one of the first choices for management of refractory glaucoma in childhood.