July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Modulation of endothelial cell function and pathologic ocular angiogenesis by microRNA-145
Author Affiliations & Notes
  • Chi-Hsiu Liu
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • Zhongxiao Wang
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • Ye Sun
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • Rubi Duran
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • Alexander Poblete
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • Steve S Cho
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • Jing Chen
    Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Chi-Hsiu Liu, None; Zhongxiao Wang, None; Ye Sun, None; Rubi Duran, None; Alexander Poblete, None; Steve Cho, None; Jing Chen, None
  • Footnotes
    Support  This work was supported by the Knights Templar Eye Foundation (to CHL), and NIH/NEI (R01 024963 and R01 028100), Mass Lions Eye Research Fund Inc., BrightFocus Foundation and Research to Prevent Blindness (to JC).
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 762. doi:
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    • Get Citation

      Chi-Hsiu Liu, Zhongxiao Wang, Ye Sun, Rubi Duran, Alexander Poblete, Steve S Cho, Jing Chen; Modulation of endothelial cell function and pathologic ocular angiogenesis by microRNA-145. Invest. Ophthalmol. Vis. Sci. 2018;59(9):762.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Pathologic ocular angiogenesis is a major cause of blindness in several vascular eye diseases including proliferative retinopathy. It is critical to identify factors dysregulated in retinas with pathologic neovessels, in order to develop effective targeted therapeutics. MicroRNAs are a group of small regulatory RNAs that control many biological processes including angiogenesis. Previously we discovered that multiple microRNAs, including miR-145, were dysregulated in a mouse model of oxygen-induced proliferative retinopathy (OIR). Here we investigated the specific role of miR-145 in regulating vascular endothelial cell (EC) function and pathologic ocular angiogenesis in mice.

Methods : To induce pathologic ocular angiogenesis in OIR, neonatal mice were exposed to 75% O2 from postnatal day (P) 7 to 12. Expression levels of miR-145 were analyzed in P17 OIR retinas compared with room air control retinas. MiR-145 inhibitor and negative control were injected intreavitreally in contralateral eyes of OIR mice, followed by quantification of pathologic retinal neovascularization (NV) and vaso-obliteration (VO) at P17. Effects of miR-145 on endothelial cell function were analyzed in human retinal microvascular endothelial cell (HRMEC) culture treated with miR-145 inhibitor, mimic and negative control. Putative target genes of miR-145 were predicted by complementary sequence analysis, followed by verification in both retinas and HRMECs.

Results : Expression of miR-145 was significantly upregulated (>2-fold increase) in P17 OIR retinas with pathologic NV compared with the normoxic controls. Intravitreal injection of miR-145 inhibitor significantly decreased pathologic NV by ~50% in OIR, without affecting VO. In consistence with increased miR-145 levels, putative target genes (Klf4, Pak1, Tmem9b, Tmod3, and Trio) were shown decreased expression in OIR retinas. Inhibition of miR-145 in HRMECs substantially decreased EC angiogenic function including proliferation, migration, and tubular formation, and increased expression of the target genes. Moreover, HRMECs treated with miR-145 mimic increased vascular EC function and downregulated of the target genes.

Conclusions : Our findings indicate that miR-145 is a novel pro-angiogenic regulator of vascular EC function and pathologic ocular NV. Inhibition of miR-145 may serve as a potential therapeutic approach to develop treatments for neovascular eye diseases.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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