Photoelectric Dye, NK-5962, as a Potential Drug for Preventing Retinal Neurons from Apoptosis: Pharmacokinetic Studies Based on Review of the Evidence

Author:

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

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 concentrations 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.

Funder

Japan Agency for Medical Research and Development

Publisher

MDPI AG

Subject

Paleontology,Space and Planetary Science,General Biochemistry, Genetics and Molecular Biology,Ecology, Evolution, Behavior and Systematics

Reference35 articles.

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2. Immobilization of photoelectric dye on the polyethylene film surface;Uchida,2005

3. Photoelectric Dye-coupled Polyethylene Film as a Prototype of Retinal Prostheses

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