July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
MicroRNA-143 plays a protective role in ischemia-induced retinal neovascularization
Author Affiliations & Notes
  • Guei-Sheung Liu
    Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
    Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Victoria, Australia
  • Jiang-Hui Wang
    Centre for Eye Research Australia, East Melbourne, Victoria, Australia
    Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Victoria, Australia
  • Jinying Chen
    Department of Ophthalmology, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
    Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
  • Leilei Tu
    Department of Ophthalmology, the First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
  • Vikrant Singh
    Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
  • Moeen Riaz
    Public Health Genomics, School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
  • Fan Li
    Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
    State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yat-sen University, Guangzhou, Guangdong, China
  • Alex W Hewitt
    Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia
    Centre for Eye Research Australia, East Melbourne, Victoria, Australia
  • Peter van Wijngaarden
    Centre for Eye Research Australia, East Melbourne, Victoria, Australia
    Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Victoria, Australia
  • Gregory J. Dusting
    Centre for Eye Research Australia, East Melbourne, Victoria, Australia
    Ophthalmology, Department of Surgery, University of Melbourne, East Melbourne, Victoria, Australia
  • Footnotes
    Commercial Relationships   Guei-Sheung Liu, None; Jiang-Hui Wang, None; Jinying Chen, None; Leilei Tu, None; Vikrant Singh, None; Moeen Riaz, None; Fan Li, None; Alex Hewitt, None; Peter van Wijngaarden, None; Gregory J. Dusting, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3261. doi:https://doi.org/
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      Guei-Sheung Liu, Jiang-Hui Wang, Jinying Chen, Leilei Tu, Vikrant Singh, Moeen Riaz, Fan Li, Alex W Hewitt, Peter van Wijngaarden, Gregory J. Dusting; MicroRNA-143 plays a protective role in ischemia-induced retinal neovascularization. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3261. doi: https://doi.org/.

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

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Abstract

Purpose : Retinal neovascularization is a severe complication of retinopathy of prematurity and proliferative diabetic retinopathy. MicroRNAs (miRNAs) are master regulators of gene expression that play important roles in retinal neovascularization. Here, we defined the expression profile of retinal miRNA and investigated the role of miRNA-143 in a rat model of oxygen-induced retinopathy (OIR).

Methods : Rat pups were subjected to cyclic hyperoxia or normoxia (control) for 14 days, after which retinal RNA was isolated for miRNA profiling by next-generation sequencing (miRNA-Seq). To validate the identified miRNAs, synthetic miRNA mimics were administrated intravitreally to rats with OIR at postnatal day (P) 14. Retinal vascular remodelling was assessed 4 days later at P18. The role of miRNA-143 and its molecular network mediating retinal neovascularization were analyzed by RNA-Seq and bioinformatics analysis. A downstream target of miRNA-143 was inhibited as a potential treatment for neovascularization in OIR rat.

Results : Four miRNAs, miR-143-3p, miR-126-3p, miR-150-5p and miR-145-5p, were down-regulated in the OIR rat retina compared to normoxic rats. Of these identified miRNAs, miR-143 is enriched in the retina and was first reported being associated with retinal neovascularization. Restoration of the down-regulated miRNAs by intravitreal delivery of miR-143, miR-126 or miR-150 mimics significantly suppressed retinal neovascularization in OIR rats. RNA-Seq revealed that miR-143 alleviated retinal neovascularization by regulating angiogenesis/inflammation pathways via fos signalling. Moreover, computational analysis indicated that a miRNA-143-targeted gene, transforming growth factor-beta activated kinase 1 (TAK1), is involved in several key pathways associated with retinal neovascularization and dysregulated miRNAs. Genetic and pharmacological inhibition of TAK1 suppressed retinal neovascularization and vascular inflammation in OIR rats.

Conclusions : Our data highlight the utility of next-generation sequencing for the development of therapeutics for retinal neovascularization and indicate that miR-143 plays a protective role against ischemia-induced retinal neovascularization.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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