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Neutralization of Bombina variegata peptide 8 suppresses retinal neovascularization in two different murine models: The oxygen-induced retinopathy model and the rhodopsin promoter/VEGF transgenic mouse model.

Abstract
Bombina variegata 8 (Bv8), also known as prokineticin-2 (PK-2), is a potent pro-angiogenic factor. However, its role in retinal neovascularization (RNV) remains unknown. In this study, we explored the role of Bv8 in the pathogenesis of RNV. We found that the expression of Bv8 was significantly increased in two different models of retinal neovascularization: the oxygen-induced retinopathy (OIR) mouse model and the rhodopsin promoter (rho)/VEGF transgenic mouse model. Neutralization of Bv8 by intravitreal injections of its antibody, not only inhibited retinal and subretinal neovascularization but also decreased the mRNA and protein levels of several pro-angiogenic factors. Our in vitro assay showed that recombinant human Bv8 (RhBv8) protein promoted human retinal microvascular endothelial cells (HRECs) tube-formation, cell proliferation and vascular endothelial growth factor receptor 1 (VEGFR1) and receptor 2 (VEGFR2) expression. Our findings suggest that Bv8 could be used as a novel target for the treatment of RNV-related ocular diseases.
AuthorsYiyun Yao, Yixuan Yao, Anna M Demetriades, Ailing Sui, Ting Su, Yanji Zhu, Xi Shen, Bing Xie
JournalExperimental eye research (Exp Eye Res) Vol. 193 Pg. 107993 (04 2020) ISSN: 1096-0007 [Electronic] England
PMID32147400 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2020 Elsevier Ltd. All rights reserved.
Chemical References
  • Amphibian Proteins
  • Bv8 protein, Bombina variegata
  • Neuropeptides
  • Vascular Endothelial Growth Factor A
  • RNA
  • Rhodopsin
  • Oxygen
Topics
  • Amphibian Proteins (genetics, metabolism)
  • Animals
  • Animals, Newborn
  • Cell Proliferation
  • Disease Models, Animal
  • Gene Expression Regulation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuropeptides (genetics, metabolism)
  • Oxygen (toxicity)
  • Promoter Regions, Genetic
  • RNA (genetics)
  • Retinal Neovascularization (drug therapy, metabolism, pathology)
  • Retinal Vessels (metabolism)
  • Rhodopsin (metabolism)
  • Vascular Endothelial Growth Factor A (metabolism)

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