Forkhead domain inhibitory-6 attenuates subconjunctival fibrosis in rabbit model with trabeculectomy
Forkhead domain inhibitory-6 attenuates subconjunctival fibrosis in rabbit model with trabeculectomy
复制标题
Forkhead 结构域抑制 6 可减轻小梁切除术兔模型中的结膜下纤维化
DOI：
10.1016/j.exer.2021.108725
复制
发表时间：
2021-08-11
影响因子：
3.4
通讯作者：
Fan, Ning
中科院分区：
文献类型：
--
作者：
Lan, Chunlin;Tan, Junkai;Fan, Ning
抗增殖治疗对于提高青光眼滤过手术的成功率至关重要。在这项研究中，我们研究了Forkhead Domain Inhibitor-6（FDI-6）抑制小梁切除术后结膜下纤维化的潜在疗效。在体外，FDI-6（10 μ M）对纤维化反应及其潜在机制的影响进行了研究，在兔Tenon的成纤维细胞（RTF）处理或不转化生长因子-β 1（TGF-β 1，20 ng/mL）。在体内，将FDI-6（40 μ M）结膜下注射到兔小梁切除术模型中。术后14天内监测眼内压（IOP）变化。手术区域的滤过泡形态和上皮下纤维化通过裂隙灯和共聚焦显微镜检查以及组织学检查进行评价。结果显示，在细胞培养研究中，FDI-6通过下调TGF-β 1/Smad 2/3信号通路抑制TGF-β处理的RTFs的增殖、迁移、胶原凝胶收缩以及纤维连接蛋白（FN）和α-平滑肌肌动蛋白（α-SMA）的表达水平。在动物研究中，小梁切除术后，FDI-6治疗组的IOP显著低于盐水治疗组。与盐水治疗的眼睛相比，FDI-6治疗的眼睛显示出更好的滤过泡外观，血管更少。体内共聚焦显微镜和组织病理学分析显示，与对照组相比，FDI-6治疗组小梁切除术后结膜下纤维化显著减弱。总之，我们的研究表明，FDI-6对小梁切除术引起的结膜下纤维化具有抑制作用，有望成为未来抗青光眼滤过手术中使用的新的抗增殖剂。
Antiproliferative therapies are crucially important for improving the success rate of the glaucoma filtration surgeries. In this study, we investigated the potential efficacy of Forkhead Domain Inhibitory-6 (FDI-6) in inhibiting post-trabeculectomy subconjunctival fibrosis. In vitro, the effect of FDI-6 (10 mu M) on fibrotic response and its underlying mechanism were investigated in rabbit tenon's fibroblasts (RTFs) treated with or without transforming growth factor-beta 1 (TGF-beta 1, 20 ng/mL). In vivo, FDI-6 (40 mu M) was injected subconjunctivally to a rabbit trabeculectomy model. Intraocular pressure (IOP) changes were monitored within the 14-day period postsurgery. Bleb morphology and subepithelial fibrosis at the operating area were evaluated with slit lamp and confocal microscopic examinations and with histologic examinations. The results showed that, in cell culture studies, FDI-6 suppressed the proliferation, migration, collagen gel contraction and the expression levels of fibronectin (FN) and alpha-smooth muscle actin (alpha-SMA) in RTFs with TGF-beta treatment by down-regulating the TGF beta 1/Smad2/3 signaling pathway. In animal studies, the IOPs of the FDI-6-treated group were significantly lower than those of the saline-treated group after trabeculectomy. The FDI-6-treated eyes showed a better bleb appearance with fewer blood vessels compared to the saline-treated eyes. The analysis of confocal microscopy in vivo and histopathology revealed that subconjunctival fibrosis after trabeculectomy was significantly attenuated in the FDI-6-treated group compared to the controls. In conclusion, our studies indicate that FDI-6 exerts an inhibitory effect on subconjunctival fibrosis caused by trabeculectomy, holding potentials as a new antiproliferative agent used in anti-glaucoma filtration surgeries in the future.