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 μM) on fibrotic response and its underlying mechanism were investigated in rabbit tenon's fibroblasts (RTFs) treated with or without transforming growth factor-β1 (TGF-β1, 20 ng/mL). In vivo, FDI-6 (40 μM) was injected subconjunctivally to a rabbit trabeculectomy model. Intraocular pressure (IOP) changes were monitored within the 14-day period post-surgery. 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 α-smooth muscle actin (α-SMA) in RTFs with TGF-β treatment by down-regulating the TGF-β1/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.

抗增殖疗法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 Inhibitory-6 (FDI-6) 在抑制小梁切除术后结膜下纤维化方面的潜在功效。在体外，在用或不用转化生长因子-β1 (TGF-β1, 20 ng/mL) 处理的兔腱成纤维细胞 (RTF) 中研究了 FDI-6 (10 μM) 对纤维化反应的影响及其潜在机制。在体内，将 FDI-6 (40 μM) 结膜下注射到兔小梁切除术模型中。在术后 14 天内监测眼压 (IOP) 变化。使用裂隙灯和共聚焦显微镜检查以及组织学检查评估手术区域的气泡形态和上皮下纤维化。结果表明，在细胞培养研究中，FDI-6 通过 TGF-β 处理抑制了 RTFs 的增殖、迁移、胶原凝胶收缩以及纤连蛋白 (FN) 和 α-平滑肌肌动蛋白 (α-SMA) 的表达水平。下调 TGF-β1/Smad2/3 信号通路。在动物研究中，小梁切除术后 FDI-6 治疗组的眼压明显低于盐水治疗组。与盐水处理的眼睛相比，FDI-6 处理的眼睛显示出更好的气泡外观和更少的血管。体内共聚焦显微镜和组织病理学分析表明，与对照组相比，FDI-6 治疗组小梁切除术后结膜下纤维化显着减弱。综上所述，