Topical application of TAK1 inhibitor encapsulated by gelatin particle alleviates corneal neovascularization
Jiang-Hui Wang, Ching‐Li Tseng, Fan‐Li Lin, Jinying Chen, Erh-Hsuan Hsieh, S Lama, Yu-Fan Chuang, Satheesh Kumar, Linxin Zhu, Myra B. McGuinness, Jessika Hernandez, Leilei Tu, Peng‐Yuan Wang, Guei‐Sheung Liu
Abstract
Rationale: Corneal neovascularization (CoNV) is a severe complication of various types of corneal diseases, that leads to permanent visual impairment. Current treatments for CoNV, such as steroids or anti-vascular endothelial growth factor agents, are argued over their therapeutic efficacy and adverse effects. Here, we demonstrate that transforming growth factor- (TGF-)-activated kinase 1 (TAK1) plays an important role in the pathogenesis of CoNV. Methods: Angiogenic activities were assessed in ex vivo and in vitro models subjected to TAK1 inhibition by 5Z-7-oxozeaenol, a selective inhibitor of TAK1. RNA-Seq was used to examine pathways that could be potentially affected by TAK1 inhibition. A gelatin-nanoparticles-encapsulated 5Z-7-oxozeaenol was developed as the eyedrop to treat CoNV in a rodent model.