May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Anti–angiogenic effects of fasudil/hydroxyfasudil, a specific Rho–kinase inhibitor.
Author Affiliations & Notes
  • M. Miura
    Department of Ophthalmology, Kyushu university, Fukuoka, Japan
  • Y. Hata
    Department of Ophthalmology, Kyushu university, Fukuoka, Japan
  • Y. Noda
    Department of Ophthalmology, Kyushu university, Fukuoka, Japan
  • K. Hirayama
    Department of Ophthalmology, Kyushu university, Fukuoka, Japan
  • S. Nakao
    Department of Ophthalmology, Kyushu university, Fukuoka, Japan
  • T. Ishibashi
    Department of Ophthalmology, Kyushu university, Fukuoka, Japan
  • Footnotes
    Commercial Relationships  M. Miura, None; Y. Hata, Asahi Kasei Pharma F; Y. Noda, None; K. Hirayama, None; S. Nakao, None; T. Ishibashi, None.
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 1916. doi:
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    • Get Citation

      M. Miura, Y. Hata, Y. Noda, K. Hirayama, S. Nakao, T. Ishibashi; Anti–angiogenic effects of fasudil/hydroxyfasudil, a specific Rho–kinase inhibitor. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1916.

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

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Abstract

Abstract: : Purpose: To investigate the anti–angiogenic effects of fasudil/hydroxyfasudil, a specific Rho–kinase inhibitor, both in vitro and in vivo. Methods: Bovine retinal capillary endothelial cells (BRECs) were used for in vitro experiments. Vascular endothelial growth factor (VEGF)–dependent phosphorylation of VEGFR2 and myosin light chain (MLC) was analyzed by western blotting using BRECs’ total cell lysates. The effects of VEGF on the cell growth, migration and in vitro tube formation were evaluated by [3H]–thymidine uptake, boyden chamber assay and in vitro tube formation assay using type I collagen gel model, respectively. VEGF–dependent in vivo angiogenesis was analyzed by mouse corneal pocket assay. Results: While VEGF stimulated the phosphorylation of VEGFR2 in BRECs within 5 mins, no significant inhibitory effect was observed in the presence of hydroxyfasudil at the concentration examined. VEGF transiently dephosphorylated MLC in BRECs within 5 mins and significantly increased the phosphorylation state of MLC thereafter. Hydroxyfasudil attenuated VEGF–dependent phosphorylation of MLC in a dose dependent fashion, and almost complete attenuation was detected at a concentration of 20µM without affecting VEGFR2 phosphorylation. 20µM of hydroxyfasudil significantly prohibited VEGF–dependent BRECs’ growth, migration and in vitro tube formation as well. VEGF–induced corneal neovascularization was almost completely prohibited by co–embedding the VEGF with fasudil in the corneal pockets. Conclusions: A specific Rho–kinase inhibitor fasudil/hydroxyfasudil, which is already in clinical use for the treatment of cerebral vasospasm, might have therapeutic potential for the treatment of angiogenic diseases.

Keywords: diabetic retinopathy • neovascularization 
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