Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization

Chi Hsiu Liu, Ye Sun, Jie Li, Yan Gong, Katherine T. Tian, Lucy P. Evans, Peyton C. Morss, Thomas W. Fredrick, Nicholas J. Saba, Jing Chen, Jeremy Nathans

Research output: Contribution to journalArticlepeer-review

Abstract

Pathologic ocular neovascularization commonly causes blindness. It is critical to identify the factors altered in pathologically proliferating versus normally quiescent vessels to develop effective targeted therapeutics. MicroRNAs regulate both physiological and pathological angiogenesis through modulating expression of gene targets at the posttranscriptional level. However, it is not completely understood if specific microRNAs are altered in pathologic ocular blood vessels, influencing vascular eye diseases. Here we investigated the potential role of a specific microRNA, miR-150, in regulating ocular neovascularization. We found that miR-150 was highly expressed in normal quiescent retinal blood vessels and significantly suppressed in pathologic neovessels in a mouse model of oxygen-induced proliferative retinopathy. MiR-150 substantially decreased endothelial cell function including cell proliferation, migration, and tubular formation and specifically suppressed the expression of multiple angiogenic regulators, CXCR4, DLL4, and FZD4, in endothelial cells. Intravitreal injection of miR-150 mimic significantly decreased pathologic retinal neovascularization in vivo in both wild-type and miR-150 knockout mice. Loss of miR-150 significantly promoted angiogenesis in aortic rings and choroidal explants ex vivo and laser-induced choroidal neovascularization in vivo. In conclusion, miR-150 is specifically enriched in quiescent normal vessels and functions as an endothelium-specific endogenous inhibitor of pathologic ocular neovascularization.

Original languageEnglish (US)
Pages (from-to)12163-12168
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number39
DOIs
StatePublished - Sep 29 2015

Keywords

  • Endothelial cells
  • MiR-150
  • MicroRNA
  • Neovascularization
  • Retinopathy

ASJC Scopus subject areas

  • General

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