Evaluation of nintedanib efficacy: Attenuating the lens fibrosis in vitro and vivo

Purpose: 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.

Conclusion: Nintedanib alleviates fibrotic cataracts by suppressing the TGFβ2/ Smad and non-Smad signaling pathways. Nintedanib is a potential drug for lens fibrosis.

Cataract; Epithelial-mesenchymal transition; Fibrosis; Nintedanib; TGFβ2.