June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
A new class of RNA interference therapeutic agent against (pro)renin receptor suppresses choroidal neovascularization
Author Affiliations & Notes
  • Ye Liu
    Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine;Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
    Department of Ophthalmology, The Fourth Affiliated Hospital of China Medical University, China Medical University, Shenyang, China., Shenyang, Liaoning, China
  • Atsuhiro Kanda
    Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine;Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
  • Erdal Tan Ishizuka
    Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine;Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
  • Di Wu
    Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine;Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
  • Kousuke Noda
    Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine;Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
  • Susumu Ishida
    Laboratory of Ocular Cell Biology and Visual Science, Hokkaido University Graduate School of Medicine;Department of Ophthalmology, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan
  • Footnotes
    Commercial Relationships   Ye Liu, None; Atsuhiro Kanda, None; Erdal Ishizuka, None; Di Wu, None; Kousuke Noda, None; Susumu Ishida, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4075. doi:
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      Ye Liu, Atsuhiro Kanda, Erdal Tan Ishizuka, Di Wu, Kousuke Noda, Susumu Ishida; A new class of RNA interference therapeutic agent against (pro)renin receptor suppresses choroidal neovascularization. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4075.

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

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Abstract

Purpose : To investigate the effect of a novel single-stranded RNA interference (RNAi) agent targeting (pro)renin receptor [(P)RR]/ATP6AP2, (P)RR-PshRNA, on attenuation of choroidal neovascularization (CNV).

Methods : Laser photocoagulation was performed to induce CNV in C57BL/6J mice, followed by intravitreal injection of (P)RR- or control-PshRNA. Seven days after laser injury, choroidal flat mounts were prepared and the size of the CNV lesions was quantified. The retinal pigment epithelium (RPE)-choroid complex was harvested 3 days after laser injury and the levels of (P)RR/Atp6ap2 and inflammation-associated molecules (e.g., tumor necrosis factor-α, adhesion G protein-coupled receptor E1 (also known as F4/80), interleukin-6, monocyte chemotactic protein-1, intercellular adhesion molecule-1) were analyzed using real-time qPCR.

Results : Real-time qPCR showed that the levels of (P)RR/ATP6AP2 mRNA significantly decreased following exposure to human RPE and mouse endothelial cells with (P)RR-PshRNA as well as a conventional double-stranded (P)RR-siRNA. Compared to the mice treated with control-PshRNA or PBS, the mice treated with intravitreal injection of (P)RR-PshRNA showed a significant attenuation of CNV size in a dose-dependent manner (p < 0.05), and a notable decrease in the mRNA levels of (P)RR/Atp6ap2 and inflammation-associated molecules in the RPE-choroid complex (p < 0.05).

Conclusions : (P)RR-PshRNA, a novel single-stranded RNAi agent targeting human and mouse (P)RR/ATP6AP2, can reduce expression of inflammation-associated molecules and suppress CNV formation. Our data suggest the possibility that (P)RR-PshRNA can be used for neovascular age-related macular degeneration as a novel therapeutic agent.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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