The Sustained Release of Tafluprost with a Drug Delivery System Prevents the Axonal Injury-induced Loss of Retinal Ganglion Cells in Rats

Kota Sato, Yurika Nakagawa, Kazuko Omodaka, Hiroyuki Asada, Shinobu Fujii, Kenji Masaki, Toru Nakazawa

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To investigated whether a new drug delivery system (DDS) could enable the controlled release of tafluprost and suppress retinal ganglion cell (RGC) death in rats after optic nerve transection (ONT). Methods: A DDS containing 0.04%, 0.20% or 1.00% tafluprost, or vehicle, was injected intravitreally in 8-12-week-old male Sprague-Dawley rats 7 days before ONT, and the retinas were extracted 7 days after ONT. For comparison, eye drops containing 0.0015% tafluprost or vehicle were used once a day. The extracted retinas were analyzed with liquid chromatography–tandem mass spectrometry, immunohistochemistry and western blotting. Results: The level of tafluprost acid in the groups that received the 0.20% and 1.00% tafluprost DDSs was stable, and higher than the maximum concentration in the eye drop group, even after 14 days. In the retinas treated with the 1.00% tafluprost DDS, the active form of the drug had a high concentration (~50 times higher than eye drops), but no significant IOP difference compared with its vehicle in this study. The 1.00% tafluprost DDS group also had less cleaved α-fodrin and fewer c-Jun-positive cells than the vehicle DDS group. Conclusions: This study found that a newly developed DDS allowed the controlled release of tafluprost and prevented the loss of RGCs after ONT IOP independently. The duration of drug action on the target site was longer with a tafluprost DDS than with topical instillation and should therefore reduce problems related to lack of patient compliance. This system may also enable new treatments to prevent RGC degeneration in diseases such as glaucoma.

Original languageEnglish
Pages (from-to)1114-1123
Number of pages10
JournalCurrent Eye Research
Volume45
Issue number9
DOIs
Publication statusPublished - 2020 Sep 1

Keywords

  • Drug delivery system
  • neuroprotection
  • optic nerve transection
  • retinal ganglion cell
  • tafluprost

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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