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Inhibition of choroidal fibrovascular membrane formation by new class of RNA interference therapeutic agent targeting periostin

Gene Therapy volume 22, pages 127–137 (2015)Cite this article

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Abstract

Age-related macular degeneration (AMD) is a vision-threatening disease characterized by choroidal fibrovascular membrane (FVM) formation, choroidal neovascularization (CNV) and choroidal fibrosis. No safe and effective therapeutic method has been developed for the choroidal fibrosis, although anti-vascular endothelial growth factor therapy can partially shrink the CNV. We recently reported that periostin (POSTN), which is produced by retinal pigment epithelial cells, has an important role in the formation of preretinal FVMs, but its role in choroidal FVMs has not been determined. In this study, we used Postn knockout mice to investigate the role played by POSTN in choroidal FVM formation. In addition, we used a new class of RNA interference (RNAi) agent (NK0144) that targets POSTN and determined its effect on choroidal FVM development. Genetic ablation of Postn had an inhibitory effect not only on CNV formation but also on choroidal fibrosis in a mouse CNV model. NK0144 also had a greater inhibitory effect on both the CNV and choroidal fibrosis than control RNAi with no apparent adverse effects. These findings suggest a causal relationship between POSTN and choroidal FVM formation, and also a potential therapeutic role of intravitreal NK0144 for AMD.

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Acknowledgements

We thank the staff of the Research Support Center (Graduate School of Medical Sciences, Kyushu University) for technical support and Masayo Eto, Kinuko Sasada and Hiroko Miura for their excellent technical assistance. This work was supported in part by JSPS KAKENHI grant numbers 24249083, 23592574, 26293374, 26670757, Takeda Science Foundation, and Adaptable and Seamless Technology Transfer Program through Target-driven R&D from the Japan Science and Technology Agency. T Nakama is supported by a fellowship from the Japan Society for the Promotion of Science for Young Scientists.

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Authors and Affiliations

  1. Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan

    T Nakama, S Yoshida, K Ishikawa, Y Kobayashi, Y Zhou, S Nakao, Y Sassa, Y Oshima & T Ishibashi

  2. Department of Ophthalmology, Fukuoka University Chikushi Hospital, Fukuoka, Japan

    Y Sassa

  3. AQUA Therapeutics Co., Ltd., Kobe, Japan

    K Takao, A Shimahara & K Yoshikawa

  4. Strategic Headquarters for Research and Development, BONAC Corporation, BIO Factory, Fukuoka, Japan

    T Hamasaki, T Ohgi & H Hayashi

  5. Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan

    A Matsuda

  6. Department of Biological Information, Tokyo Institute of Technology, Yokohama, Japan

    A Kudo

  7. Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan

    M Nozaki & Y Ogura

  8. Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan

    M Kuroda

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Corresponding author

Correspondence to S Yoshida.

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Competing interests

The patent on periostin (WPO Patent WO/2013/147140) became public, and in these patents, the names of TN, SY, KI, TH, TO and TI are included.

This work was supported in part by A-STEP (Adaptable & Seamless Technology Transfer Program through Target-driven R&D) governed by Japan Science and Technology Agency.

SY is supported by JSPS 26293374.

KT, AS and KY are employees of AQUA Therapeutics and hold equity.

TH, TO and HH are employees of BONAC Corporation and hold equity.

The remaining authors declare no conflict of interest.

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Nakama, T., Yoshida, S., Ishikawa, K. et al. Inhibition of choroidal fibrovascular membrane formation by new class of RNA interference therapeutic agent targeting periostin. Gene Ther 22, 127–137 (2015). https://doi.org/10.1038/gt.2014.112

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