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

T. Nakama, S. Yoshida, K. Ishikawa, Y. Kobayashi, Y. Zhou, S. Nakao, Y. Sassa, Y. Oshima, K. Takao, A. Shimahara, K. Yoshikawa, T. Hamasaki, T. Ohgi, H. Hayashi, A. Matsuda, A. Kudo, M. Nozaki, Y. Ogura, M. Kuroda, T. Ishibashi

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)127-137
Number of pages11
JournalGene Therapy
Volume22
Issue number2
DOIs
Publication statusPublished - Feb 7 2015

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Choroidal Neovascularization
RNA Interference
Fibrosis
Membranes
Macular Degeneration
Choroid Diseases
Therapeutics
Retinal Pigments
Knockout Mice
Vascular Endothelial Growth Factor A
Epithelial Cells
Inhibition (Psychology)

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

Inhibition of choroidal fibrovascular membrane formation by new class of RNA interference therapeutic agent targeting periostin. / Nakama, T.; Yoshida, S.; Ishikawa, K.; Kobayashi, Y.; Zhou, Y.; Nakao, S.; Sassa, Y.; Oshima, Y.; Takao, K.; Shimahara, A.; Yoshikawa, K.; Hamasaki, T.; Ohgi, T.; Hayashi, H.; Matsuda, A.; Kudo, A.; Nozaki, M.; Ogura, Y.; Kuroda, M.; Ishibashi, T.

In: Gene Therapy, Vol. 22, No. 2, 07.02.2015, p. 127-137.

Research output: Contribution to journalArticle

Nakama, T, Yoshida, S, Ishikawa, K, Kobayashi, Y, Zhou, Y, Nakao, S, Sassa, Y, Oshima, Y, Takao, K, Shimahara, A, Yoshikawa, K, Hamasaki, T, Ohgi, T, Hayashi, H, Matsuda, A, Kudo, A, Nozaki, M, Ogura, Y, Kuroda, M & Ishibashi, T 2015, 'Inhibition of choroidal fibrovascular membrane formation by new class of RNA interference therapeutic agent targeting periostin', Gene Therapy, vol. 22, no. 2, pp. 127-137. https://doi.org/10.1038/gt.2014.112
Nakama, T. ; Yoshida, S. ; Ishikawa, K. ; Kobayashi, Y. ; Zhou, Y. ; Nakao, S. ; Sassa, Y. ; Oshima, Y. ; Takao, K. ; Shimahara, A. ; Yoshikawa, K. ; Hamasaki, T. ; Ohgi, T. ; Hayashi, H. ; Matsuda, A. ; Kudo, A. ; Nozaki, M. ; Ogura, Y. ; Kuroda, M. ; Ishibashi, T. / Inhibition of choroidal fibrovascular membrane formation by new class of RNA interference therapeutic agent targeting periostin. In: Gene Therapy. 2015 ; Vol. 22, No. 2. pp. 127-137.
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