Photoelectric dye, nk-5962, as a potential drug for preventing retinal neurons from apoptosis: Pharmacokinetic studies based on review of the evidence

Toshihiko Matsuo, Shihui Liu, Tetsuya Uchida, Satomi Onoue, Shinsaku Nakagawa, Mayumi Ishii, Kayoko Kanamitsu

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

NK-5962 is a key component of photoelectric dye-based retinal prosthesis (OUReP). In testing the safety and efficacy, NK-5962 was safe in all tests for the biological evaluation of medical devices (ISO 10993) and effective in preventing retinal cells from death even under dark conditions. The long-term implantation of the photoelectric dye-coupled polyethylene film in the subretinal space of hereditary retinal dystrophic (RCS) rats prevented neurons from apoptosis in the adjacent retinal tissue. The intravitreous injection of NK-5962 in the eyes of RCS rats, indeed, reduced the number of apoptotic cells in the retinal outer nuclear layer irrespective of light or dark conditions. In this study, we reviewed the in vitro and in vivo evidence of neuroprotective effect of NK-5962 and designed pharmacokinetic experiments. The in vitro IC50 of 1.7 μM, based on the protective effect on retinal cells in culture, could explain the in vivo EC50 of 3 μM that is calculated from con-centrations of intravitreous injection to prevent retinal neurons from apoptosis. Pharmacokinetics of NK-5962 showed that intravenous administration, but not oral administration, led to the effective concentration in the eye of rats. NK-5962 would be a candidate drug for delaying the deterioration of retinal dystrophy, such as retinitis pigmentosa.

Original languageEnglish
Article number591
JournalLife
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 2021

Keywords

  • ADME
  • Apoptosis
  • NK-5962
  • Neuroprotection
  • Pharmacokinetics
  • Photoelectric dye
  • Photosafety
  • Phototoxic/photosensitive assay
  • Reactive oxygen species assay
  • Retinal neuron

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Biochemistry, Genetics and Molecular Biology(all)
  • Space and Planetary Science
  • Palaeontology

Fingerprint

Dive into the research topics of 'Photoelectric dye, nk-5962, as a potential drug for preventing retinal neurons from apoptosis: Pharmacokinetic studies based on review of the evidence'. Together they form a unique fingerprint.

Cite this