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Title: Inhibition of TBK1 reduces choroidal neovascularization in vitro and in vivo

Journal Article · · Biochemical and Biophysical Research Communications
 [1];  [2];  [3];  [4];  [5]; ; ;  [4]
  1. School of Medicine, Nantong University, Nantong, 226001, Jiangsu (China)
  2. Nantong University, Nantong, Jiangsu (China)
  3. Department of Pathogen Biology, Medical College, Nantong University, Nantong, 226001, Jiangsu (China)
  4. Department of Ophthalmology, Affiliated Hospital of Nantong University, Nantong, 226001 (China)
  5. Department of Ophthalmology, The First People's Hospital of Nantong, 226001, Jiangsu Province (China)

Highlights: • The expression of TBK1 and VEGF is up-regulated in CNV model. • Knockdown of TBK1 alleviates CNV formation via inhibiting VEGF expression. • TBK1 plays a critical role in the development of CNV. choroidal neovascularization (CNV), a characteristic of wet age-related macular degeneration (AMD), causes severe vision loss among elderly patients. TANK-binding kinase 1 (TBK1) is a ubiquitously expressed serine–threonine kinase and is found to induce endothelial cells proliferation, represent a novel mediator of tumor angiogenesis and exert pro-inflammatory effect. However, the role of TBK1 in choroidal neovascularization has not been investigated so far. In this study, we found that the expression of TBK1 and VEGF was up-regulated in RF/6 A cells chemical hypoxia model and laser-induced mouse CNV model. Silencing of TBK1 suppressed the proliferation and tube formation activity of RF/6 A cells. Intravitreal injection of anti-TBK1 monoclonal antibody ameliorates CNV formation. Taken together, these findings exhibit a proangiogenic role for TBK1 via upregulating the expression of VEGF, and may suggest that TBK1 inhibition offers a unique and alternative method for prevention and treatment of AMD.

OSTI ID:
23136939
Journal Information:
Biochemical and Biophysical Research Communications, Vol. 503, Issue 1; Other Information: Copyright (c) 2018 Elsevier Inc. All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
Country of Publication:
United States
Language:
English