Effects of ripasudil, a rho kinase inhibitor, on blood flow in the optic nerve head of normal rats

  • Yasushi Wada
  • Tomomi HigashideEmail author
  • Atsushi Nagata
  • Kazuhisa Sugiyama
Basic Science



To evaluate the effect of topically administrated ripasudil, a rho kinase inhibitor, on blood flow in the optic nerve head (ONH) of normal rats.


Ripasudil (0.4%) or placebo was administered in the right eye of normal Brown Norway rats in a double-blind manner. Laser speckle flowgraphy was measured in the ONH of the right eye 20 or 40 min after a single instillation and before and after 7 or 14 days of twice daily instillation. Mean blur rate was evaluated in the total area (MA), the vessel region (MV), and the tissue region (MT). Intraocular pressure (IOP), blood pressure, ocular perfusion pressure (OPP), and heart rate were also recorded at each time point.


After a single instillation, MV was significantly larger at 40 min than 20 min in the ripasudil group (P = 0.044) and was significantly lower in the placebo group (P = 0.023). MA and MV 40 min after instillation were significantly larger in the ripasudil group than in the placebo group (P = 0.022 and P = 0.006, respectively). After continuous instillation, MA and MV in the ripasudil group significantly increased from baseline after 7 and 14 days of treatment (both P < 0.05) and MA, MV, and MT were significantly higher than in the placebo group (MA: 7 and 14 days, P < 0.01; MV: 7 days, P = 0.003, and 14 days, P = 0.012; MT: 7 days, P = 0.046). There were no significant changes in IOP, blood pressure, or OPP after single or continuous instillation.


Topical instillation of ripasudil increased blood flow around the ONH in the eyes of normal rats.


Ripasudil Laser speckle flowgraphy Rat Optic nerve head Blood flow 


Compliance with ethical standards

Conflict of interest

Kazuhisa Sugiyama has the position on advisory board of Kowa Company and has received a speaker honorarium. The other authors declare that they have no competing interests.

Animal experiments

Ethical approval: all applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of Kanazawa University (Ishikawa, no. 132712).


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of OphthalmologyKanazawa University Graduate School of Medical ScienceKanazawaJapan
  2. 2.OphthalmologyNational Hospital Organization Kanazawa Medical CenterKanazawaJapan

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