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Article

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

1
Department of Ophthalmology, Okayama University Hospital, Okayama City 700-8558, Japan
2
Okayama University Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama City 700-8558, Japan
3
Polymer Materials Science, Okayama University Graduate School of Natural Science and Technology, Okayama City 700-8530, Japan
4
Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
5
Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan
6
Drug Discovery Initiative, The University of Tokyo, Tokyo 113-0033, Japan
*
Author to whom correspondence should be addressed.
Academic Editors: Ayumi Ouchi, Yohei Tomita and Zhongjie Fu
Life 2021, 11(6), 591; https://doi.org/10.3390/life11060591
Received: 1 May 2021 / Revised: 8 June 2021 / Accepted: 17 June 2021 / Published: 21 June 2021
(This article belongs to the Special Issue Retinal Disease and Metabolism)
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. View Full-Text
Keywords: NK-5962; photoelectric dye; apoptosis; retinal neuron; neuroprotection; pharmacokinetics; ADME; phototoxic/photosensitive assay; reactive oxygen species assay; photosafety NK-5962; photoelectric dye; apoptosis; retinal neuron; neuroprotection; pharmacokinetics; ADME; phototoxic/photosensitive assay; reactive oxygen species assay; photosafety
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MDPI and ACS Style

Matsuo, T.; Liu, S.; Uchida, T.; Onoue, S.; Nakagawa, S.; Ishii, M.; Kanamitsu, K. Photoelectric Dye, NK-5962, as a Potential Drug for Preventing Retinal Neurons from Apoptosis: Pharmacokinetic Studies Based on Review of the Evidence. Life 2021, 11, 591. https://doi.org/10.3390/life11060591

AMA Style

Matsuo T, Liu S, Uchida T, Onoue S, Nakagawa S, Ishii M, Kanamitsu K. Photoelectric Dye, NK-5962, as a Potential Drug for Preventing Retinal Neurons from Apoptosis: Pharmacokinetic Studies Based on Review of the Evidence. Life. 2021; 11(6):591. https://doi.org/10.3390/life11060591

Chicago/Turabian Style

Matsuo, Toshihiko, Shihui Liu, Tetsuya Uchida, Satomi Onoue, Shinsaku Nakagawa, Mayumi Ishii, and Kayoko Kanamitsu. 2021. "Photoelectric Dye, NK-5962, as a Potential Drug for Preventing Retinal Neurons from Apoptosis: Pharmacokinetic Studies Based on Review of the Evidence" Life 11, no. 6: 591. https://doi.org/10.3390/life11060591

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