September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Protective Effects of Sustained Unoprostone Release Device in Rhodopsin Pro347Leu Transgenic Rabbits
Author Affiliations & Notes
  • Nobuhiro Nagai
    Tohoku University Graduate School of Medicine, Sendai, Japan
  • Yasuko Izumida
    Tohoku University Graduate School of Medicine, Sendai, Japan
  • Hirokazu Kaji
    Graduate School of Engineering, Tohoku University, Sendai, Japan
  • Matsuhiko Nishizawa
    Graduate School of Engineering, Tohoku University, Sendai, Japan
  • Aya Katsuyama
    Tohoku University Graduate School of Medicine, Sendai, Japan
  • Shinji Yamada
    Tohoku University Graduate School of Medicine, Sendai, Japan
  • Toru Nakazawa
    Ophthalmology, Tohoku University, Sendai, Miyagi, Japan
  • Mineo Kondo
    Mie Univ Graduate School of Med, Mie, Japan
  • Hiroko Terasaki
    Nagoya Univ School of Medicine, Nagoya, Japan
  • Yukihiko Mashima
    R-Tech Ueno, Tokyo, Japan
  • Toshiaki Abe
    Tohoku University Graduate School of Medicine, Sendai, Japan
  • Footnotes
    Commercial Relationships   Nobuhiro Nagai, US8,642,066 B2 (P); Yasuko Izumida, None; Hirokazu Kaji, US8,642,066 B2 (P); Matsuhiko Nishizawa, US8,642,066 B2 (P); Aya Katsuyama, None; Shinji Yamada, None; Toru Nakazawa, None; Mineo Kondo, None; Hiroko Terasaki, None; Yukihiko Mashima, None; Toshiaki Abe, US8,642,066 B2 (P)
  • Footnotes
    Support  JSPS KAKENHI Grant Number 26560232, 15H03015, Japan; Basic Science and Platform Technology Program for Innovative Biological Medicine, Japan; Practical Research Project for Rare/Intractable Diseases, contract grant number: 15ek0109073h0001, Japan
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4017. doi:
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      Nobuhiro Nagai, Yasuko Izumida, Hirokazu Kaji, Matsuhiko Nishizawa, Aya Katsuyama, Shinji Yamada, Toru Nakazawa, Mineo Kondo, Hiroko Terasaki, Yukihiko Mashima, Toshiaki Abe; Protective Effects of Sustained Unoprostone Release Device in Rhodopsin Pro347Leu Transgenic Rabbits. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4017.

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

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Abstract

Purpose : To evaluate the effects of sustained transscleral unoprostone isopropyl (UNO) administration for rhodopsin Pro347Leu transgenic (TG) rabbits.

Methods : We made a susteined UNO-release device (URD) consisting of a reservoir, controlled-release cover, and drug formulation, which were made of photopolymeized poly(ethyleneglycol) dimethacrylates. UNO, a prostone and BK channel activator for antiglaucoma eyedrops, was loaded in the device (length, 10 mm; width, 3.6 mm; height, 0.7 mm) at a content of 2.85 mg UNO. Six-week-old TG rabbits received episcleral implantation of URD on the right eye for 40 weeks. Electroretinogram (ERG)s and optical coherence tomography (OCT) were recorded before and after URD-implantation during successive examination.

Results : UNO release from the devices was confirmed both in vitro and in vivo for more than 24 weeks. The b-wave amplitudes of the photopic ERGs (-0.050, 0.950, 1.477, 2.000 log cds/m2) were significantly larger in the URD-treated eyes than those of placebo and non-treated eyes (P<0.05, Tukey test) during 4-32 weeks implantation. The a-wave amplitudes of photopic ERGs were also significantly larger in the URD-treated eyes than those of others at 8 and 20 weeks implantation. The b-wave amplitudes of the scotopic ERGs (-1.523, -0.523, 0.477, 1.477 log cds/m2) were significantly larger in the URD-treated eyes than those of others during 4-20 weeks implantation. The a-wave amplitudes of scotopic ERGs were significantly larger in the URD-treated eyes in some points than those of otheres. There was no siginificant difference in ERG amplitudes between placebo-treated and non-treated eyes. The thickness of the ONL measured by OCT was also significantly preserved in URD-treated eyes than those of others in some points. No side effects were observed.

Conclusions : The URD treatment could preserve the ERGs amplitudes and ONL thickness in TG rabbits as long as the URD continues to release UNO. The URD might be a promissing transscleral application.

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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