July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
The ROCK inhibitor ripasudil suppresses angio-fibrotic switch in subretinal fibrovascular proliferation
Author Affiliations & Notes
  • Iori Wada
    Kyushu university, Fukuoka, FUKUOKA, Japan
  • Shintaro Nakao
    Kyushu university, Fukuoka, FUKUOKA, Japan
  • Keijiro Ishikawa
    Kyushu university, Fukuoka, FUKUOKA, Japan
  • Muneo Yamaguchi
    Kyushu university, Fukuoka, FUKUOKA, Japan
  • Yoshihiro Kaizu
    Kyushu university, Fukuoka, FUKUOKA, Japan
  • Shigeo Yoshida
    Kyushu university, Fukuoka, FUKUOKA, Japan
  • Koh-hei Sonoda
    Kyushu university, Fukuoka, FUKUOKA, Japan
  • Footnotes
    Commercial Relationships   Iori Wada, None; Shintaro Nakao, KOWA (P); Keijiro Ishikawa, None; Muneo Yamaguchi, None; Yoshihiro Kaizu, None; Shigeo Yoshida, None; Koh-hei Sonoda, KOWA (F)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 65. doi:
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      Iori Wada, Shintaro Nakao, Keijiro Ishikawa, Muneo Yamaguchi, Yoshihiro Kaizu, Shigeo Yoshida, Koh-hei Sonoda; The ROCK inhibitor ripasudil suppresses angio-fibrotic switch in subretinal fibrovascular proliferation
      . Invest. Ophthalmol. Vis. Sci. 2018;59(9):65.

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

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Abstract

Purpose : Angio-fibrotic switch is occasionally induced during fibrosis development in neovascular age-related macular degeneration (AMD) after treatment with anti-VEGF compounds. The purpose of this study was to investigate the impact of the Rho-associated coiled coil–containing protein kinase (ROCK) inhibitor, ripasudil, on angio-fibrotic switch in subretinal fibrovasucular proliferation induced by laser injury.

Methods : C57BL/6J mice underwent retinal laser photocoagulation to induce CNV-related fibrosis. BSS (control), aflibercept (400 mg/mL), ripasudil (30 μmol/L), or the combination were administered intravitreally every three days from the 14th day after laser injury. The choroidal whole-mounts were immunofluorescently stained using α-SMA and CD31 from the 28th day after laser injury.

Results : Intravitreal treatment with ripasudil, aflibercept (IVA) or the combination of these drugs reduced the volume of the CD31-positive regions. However, intravitreal administration of ripasudil or the combination therapy, but not IVA, reduced the volume of the α-SMA-positive regions (58.4% reduction from baseline with 30 μmol/L ripasudil, p<0.01 vs control; and 53.8% reduction from baseline with combination therapy, p<0.05 vs control). Furthermore, the ratio of the maximum lengths of CD31 vs, α-SMA positive regionswas significantly decreased by IVA, but not by ripasudil or the combination therapy.

Conclusions : Anti-VEGF therapy specifically inhibited the vascular component. Importantly, the novel ROCK inhibitior, ripasudil, may have therapeutic potential in controlling angio-fibrotic switch in subretinal fibrovascular proliferation.

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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