July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Sustained release of Tafluprost with a newly developed drug delivery system protects retinal ganglion cells in rats after optic nerve transection
Author Affiliations & Notes
  • Yurika Nakagawa
    Tohoku university, Sendai, Japan
  • Kota Sato
    Tohoku university, Sendai, Japan
  • Kazuko Omodaka
    Tohoku university, Sendai, Japan
  • Toru Nakazawa
    Tohoku university, Sendai, Japan
  • Footnotes
    Commercial Relationships   Yurika Nakagawa, None; Kota Sato, Kowa Co., Ltd. (F), Santen Pharmaceutical Co., Ltd. (F), Topcon Corporation (F), Wakamoto Pharmaceutical Co., Ltd. (F); Kazuko Omodaka, Santen Pharmaceutical Co., Ltd. (F), Senju Pharmaceutical Co., Ltd. (F), Topcon Corporation (F), Wakamoto Pharmaceutical Co., Ltd. (F); Toru Nakazawa, Alcon Japan Ltd. (F), Kowa Co., Ltd. (F), Nidek Co., Ltd. (F), Otsuka Pharmaceutical Co., Ltd. (F), Santen Pharmaceutical Co., Ltd. (F), Senju Pharmaceutical Co., Ltd. (F), Topcon Corporation (F), Wakamoto Pharmaceutical Co., Ltd. (F)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 6113. doi:
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      Yurika Nakagawa, Kota Sato, Kazuko Omodaka, Toru Nakazawa; Sustained release of Tafluprost with a newly developed drug delivery system protects retinal ganglion cells in rats after optic nerve transection. Invest. Ophthalmol. Vis. Sci. 2018;59(9):6113.

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

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Abstract

Purpose : Tafluprost is a medication used in eye drops to treat open-angle glaucoma or ocular hypertension. In this study, we investigated a new drug delivery system (DDS) to enable the controlled release of Tafluprost, and determined whether this treatment could prevent retinal ganglion cell (RGC) death in rats after optic nerve transection (ONT).

Methods : This study used 7-12-week-old male Sprague-Dawley rats. To evaluate the neuroprotective effect of Tafluprost-DDS after ONT, a DDS containing 0.04%, 0.20% and 1.00% Tafluprost or vehicle per 2 μl was injected intravitreally 7 days before ONT under deep anesthesia, and the retinas were extracted 7 days after ONT. For comparison, eye drops containing 0.0015% Tafluprost (TAPROS) and vehicle were used once a day. RGC viability was determined with immunohistochemistry, using an anti-RBPMS antibody. In the eye drop group, intraocular pressure (IOP) was also measured at 0, 6 and 13 days after the start of the test. To measure the Tafluprost acid (active metabolite) level in the neural cells of the retina, a single intravitreal injection was performed of the Tafluprost DDS or vehicle. Seven days after injection, the retinas were extracted and their level was measured with liquid chromatography–tandem mass spectrometry.

Results : The Tafluprost-DDS group showed improved RGC viability. The number of RGCs was significantly higher after treatment with the Tafluprost-DDS at concentrations of 0.20% (1455 ± 151 cells/mm2) and 1.00% (1605 ± 192 cells/mm2) than after treatment with vehicle (1265 ± 182 cells/mm2). A comparison of the neuroprotective effect of TAPROS and the 0.20% Tafluprost-DDS showed that the DDS led to a significantly higher number of surviving RGCs (1391 ± 73 cells/mm2) than TAPROS (1202 ± 108 cells/mm2). IOP in the TAPROS group on days 6 and 13 decreased compared to day 0, and showed significant IOP reduction more than 6 days after the start of the test. Tafluprost acid was detected in the retina from 5 minutes to 4 hours after a single instillation of TAPROS. The level of Tafluprost acid after the DDS injection was stably maintained around the same level with the maximum concentration of TAPROS even after 7 days.

Conclusions : We showed that a newly developed Tafluprost DDS prevented the loss of RGCs after ONT. This system may enable new treatments to prevent RGC reduction in diseases such as glaucoma.

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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