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Topical application of TAK1 inhibitor encapsulated by gelatin particle alleviates corneal neovascularization.
Wang, Jiang-Hui; Tseng, Ching-Li; Lin, Fan-Li; Chen, Jinying; Hsieh, Erh-Hsuan; Lama, Suraj; Chuang, Yu-Fan; Kumar, Satheesh; Zhu, Linxin; McGuinness, Myra B; Hernandez, Jessika; Tu, Leilei; Wang, Peng-Yuan; Liu, Guei-Sheung.
Afiliación
  • Wang JH; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia.
  • Tseng CL; Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.
  • Lin FL; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
  • Chen J; Shenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • Hsieh EH; Department of Ophthalmology, the First Affiliated Hospital of Jinan University, Guangzhou, China.
  • Lama S; Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan.
  • Chuang YF; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
  • Kumar S; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
  • Zhu L; Shenzhen Key Laboratory of Biomimetic Materials and Cellular Immunomodulation, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • McGuinness MB; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
  • Hernandez J; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
  • Tu L; Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, Australia.
  • Wang PY; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, Australia.
  • Liu GS; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
Theranostics ; 12(2): 657-674, 2022.
Article en En | MEDLINE | ID: mdl-34976206
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-ß (TGF-ß)-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. Results: We showed that 5Z-7-oxozeaenol reduced angiogenic processes through impeding cell proliferation. Transcriptome analysis suggested 5Z-7-oxozeaenol principally suppresses cell cycle and DNA replication, thereby restraining cell proliferation. In addition, inhibition of TAK1 by 5Z-7-oxozeaenol blocked TNFα-mediated NFκB signalling, and its downstream genes related to angiogenesis and inflammation. 5Z-7-oxozeaenol also ameliorated pro-angiogenic activity, including endothelial migration and tube formation. Furthermore, topical administration of the gelatin-nanoparticles-encapsulated 5Z-7-oxozeaenol led to significantly greater suppression of CoNV in a mouse model compared to the free form of 5Z-7-oxozeaenol, likely due to extended retention of 5Z-7-oxozeaenol in the cornea. Conclusion: Our study shows the potential of TAK1 as a therapeutic target for pathological angiogenesis, and the gelatin nanoparticle coupled with 5Z-7-oxozeaenol as a promising new eyedrop administration model in treatment of CoNV.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Resorcinoles / Endotelio Vascular / Neovascularización de la Córnea / Quinasas Quinasa Quinasa PAM / Lactonas Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Theranostics Año: 2022 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Australia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Resorcinoles / Endotelio Vascular / Neovascularización de la Córnea / Quinasas Quinasa Quinasa PAM / Lactonas Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Theranostics Año: 2022 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Australia