September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Altered interactions of concomitant administrations of ROCK inhibitor and parasympathetic agonist in mouse IOP and outflow dynamics.
Author Affiliations & Notes
  • Reiko Yamagishi
    Ophthalmology, University of Tokyo, Bunkyo-ku, Tokyo, Japan
  • Megumi Honjo
    Ophthalmology, University of Tokyo, Bunkyo-ku, Tokyo, Japan
  • Yuka Aoyama
    Ophthalmology, University of Tokyo, Bunkyo-ku, Tokyo, Japan
  • Takatoshi Uchida
    Ophthalmology, University of Tokyo, Bunkyo-ku, Tokyo, Japan
    SENJU PHARMACEUTICAL CO., LTD. , Kobe, Japan
  • Makoto Aihara
    Ophthalmology, University of Tokyo, Bunkyo-ku, Tokyo, Japan
  • Footnotes
    Commercial Relationships   Reiko Yamagishi, None; Megumi Honjo, None; Yuka Aoyama, None; Takatoshi Uchida, SENJU PHARMACEUTICAL CO., LTD. (E); Makoto Aihara, None
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3011. doi:
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      Reiko Yamagishi, Megumi Honjo, Yuka Aoyama, Takatoshi Uchida, Makoto Aihara; Altered interactions of concomitant administrations of ROCK inhibitor and parasympathetic agonist in mouse IOP and outflow dynamics.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3011.

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

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Abstract

Purpose : Ripasudil ophthalmic solution (K115), which had been newly developed and launched as a clinically available ROCK inhibitor, shows IOP-lowering effect by enhancement of trabecular aqueous outflow. Pilocarpine (Pilo) also increases trabecular outflow but the mechanism is indirect effect on trabecular outflow different from the direct action to trabecular meshwork of the ROCK inhibitor. Pilo contract ciliary muscles whose tendon connect to trabecular meshwork leading to widening the trabecular space. Thus, it is worth clarifying the interaction of these mechanisms. In this study, we investigated the interactions of ROCK inhibitor when concomitantly applied with parasympathetic agonist, as both of which facilitate aqueous outflow from trabecular meshwork and lower intraocular pressure in mice eye and human eye.

Methods : We measured IOP with a micro needle method and evaluated aqueous dynamics at night, 30 and 60min after drug instillation. A single drop with 3 μL aliquots of saline as a control, 0.4%K115, 1%pilocarpine (Pilo) and K115+Pilo were topically applied into randomly selected one of two eyes. In addition, we evaluated the effects of each drug on cultured human trabecular meshwork cells (HTM) by the collagen gel contraction assay and immunostaining.

Results : IOP-reductions at 30min after instillation were 21.8±1.6 by a saline, 18.0±1.6 by K115, 20.9±3.2 by Pilo, 20.3±0.9 by K115+Pilo (mmHg, mean ± S.D), respectively. IOP was significantly reduced in K115 or K115+Pilo groups compared to saline group (p<0.01), however, IOP reduction of K115 group attenuated by concomitant administration with Pilo (p<0.01). In addition, there was no additive effects in IOP lowering between K115 and K115+Pilo groups at 60min after instillation. Collagen gel contraction was significantly reduced with the treatment of K115 and K115+Pilo when compared to saline treatment (p<0.01), and there were no difference between K115 and K115+Pilo treatments. Immunostaining in HTM revealed that the Pilo treatment interfere with the cytoskeletal changes caused by K115.

Conclusions : In conclusion, it was suggested that the additive IOP-lowering effect was diminished by the concomitant administration of ROCK inhibitor and parasympathetic agonist in mice eyes, possibly by interference of interactions between each drug in trabecular pathway.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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