Abstract：
OBJECTIVE: Organ fibrosis is a huge challenge in clinic. There are no drugs for fibrotic cataracts treatments in clinic. Nintedanib is approved by the FDA for pulmonary fibrosis treatments. This study aims to investigate the efficacy and mechanism of nintedanib on fibrotic cataracts.
METHODS: Drug efficacy was validated through TGFβ2-induced cell models and injury-induced anterior subcapsular cataract (ASC) mice. A slit lamp and the eosin staining technique were applied to access the degree of capsular fibrosis. The CCK-8 assay was used to evaluate the toxicity and anti-proliferation ability of the drug. The cell migration was determined by wound healing assay and transwell assay. The anti-epithelial mesenchymal transition (EMT) and anti-fibrosis efficacy were evaluated by qRT-PCR, immunoblot, and immunofluorescence. The inhibition of nintedanib to signaling pathways was certified by immunoblot.
RESULTS: Nintedanib inhibited the migration and proliferation of TGFβ2-induced cell models. Nintedanib can also repress the EMT and fibrosis of the lens epithelial cells. The intracameral injection of nintedanib can also allay the anterior subcapsular opacification in ASC mice. The TGFβ2/ Smad and non-Smad signaling pathways can be blocked by nintedanib in vitro and in vivo.
CONCLUSIONS: Nintedanib alleviates fibrotic cataracts by suppressing the TGFβ2/ Smad and non-Smad signaling pathways. Nintedanib is a potential drug for lens fibrosis.
METHODS: Drug efficacy was validated through TGFβ2-induced cell models and injury-induced anterior subcapsular cataract (ASC) mice. A slit lamp and the eosin staining technique were applied to access the degree of capsular fibrosis. The CCK-8 assay was used to evaluate the toxicity and anti-proliferation ability of the drug. The cell migration was determined by wound healing assay and transwell assay. The anti-epithelial mesenchymal transition (EMT) and anti-fibrosis efficacy were evaluated by qRT-PCR, immunoblot, and immunofluorescence. The inhibition of nintedanib to signaling pathways was certified by immunoblot.
RESULTS: Nintedanib inhibited the migration and proliferation of TGFβ2-induced cell models. Nintedanib can also repress the EMT and fibrosis of the lens epithelial cells. The intracameral injection of nintedanib can also allay the anterior subcapsular opacification in ASC mice. The TGFβ2/ Smad and non-Smad signaling pathways can be blocked by nintedanib in vitro and in vivo.
CONCLUSIONS: Nintedanib alleviates fibrotic cataracts by suppressing the TGFβ2/ Smad and non-Smad signaling pathways. Nintedanib is a potential drug for lens fibrosis.
摘要：
目的：器官纤维化在临床上是一个巨大的挑战。临床上没有用于治疗纤维变性白内障的药物。Nintedanib被FDA批准用于肺纤维化治疗。本研究旨在探讨尼达尼布治疗纤维变性白内障的疗效及作用机制。
方法：通过TGFβ2诱导的细胞模型和损伤诱导的前囊下白内障（ASC）小鼠验证药物功效。应用裂隙灯和伊红染色技术来获取囊纤维化的程度。CCK-8法用于评价药物的毒性和抗增殖能力。通过伤口愈合测定和transwell测定确定细胞迁移。通过qRT-PCR评估抗上皮间质转化（EMT）和抗纤维化的疗效，免疫印迹,和免疫荧光。免疫印迹证明了尼达尼布对信号通路的抑制作用。
结果：Nintedanib抑制TGFβ2诱导的细胞模型的迁移和增殖。Nintedanib还可以抑制晶状体上皮细胞的EMT和纤维化。前房内注射尼达尼布还可以减轻ASC小鼠的前囊膜下混浊。TGFβ2/Smad和非Smad信号通路可在体外和体内被尼达尼布阻断。
结论：尼达尼布通过抑制TGFβ2/Smad和非Smad信号通路减轻纤维化白内障。Nintedanib是治疗晶状体纤维化的潜在药物。
方法：通过TGFβ2诱导的细胞模型和损伤诱导的前囊下白内障（ASC）小鼠验证药物功效。应用裂隙灯和伊红染色技术来获取囊纤维化的程度。CCK-8法用于评价药物的毒性和抗增殖能力。通过伤口愈合测定和transwell测定确定细胞迁移。通过qRT-PCR评估抗上皮间质转化（EMT）和抗纤维化的疗效，免疫印迹,和免疫荧光。免疫印迹证明了尼达尼布对信号通路的抑制作用。
结果：Nintedanib抑制TGFβ2诱导的细胞模型的迁移和增殖。Nintedanib还可以抑制晶状体上皮细胞的EMT和纤维化。前房内注射尼达尼布还可以减轻ASC小鼠的前囊膜下混浊。TGFβ2/Smad和非Smad信号通路可在体外和体内被尼达尼布阻断。
结论：尼达尼布通过抑制TGFβ2/Smad和非Smad信号通路减轻纤维化白内障。Nintedanib是治疗晶状体纤维化的潜在药物。
