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Protective effect of P7C3 on retinal ganglion cells from optic nerve injury

  • Laboratory Investigation
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Abstract

Purpose

To determine whether P7C3-A20, a proneurogenic neuroprotective agent, can protect the retinal ganglion cells (RGCs) of rats from optic nerve crushing.

Methods

The left optic nerve of 67 rats was crushed, and 5.0 mg/kg/day of P7C3-A20 (crush-P7C3) or its vehicle (crush-placebo) was injected intraperitoneally for 3 days from one day prior to the crushing. The protective effects were determined by the number of Tuj-1-stained RGCs and by the ratio of the mRNA levels of BAX/Bcl-2 on day 7. The levels of NAD and NAD-related genes were also determined.

Results

The density of RGCs was 2009.4 ± 57.7 cells/mm2 in the sham controls; it was significantly lower in the crush-placebo group at 979.7 ± 144.3 cells/mm2 (P < 0.0001). The neuroprotective effects of P7C3-A20 was demonstrated by the significantly higher density of 1266.0 ± 193.1 cells/mm2 than in the crush-placebo group (P = 0.01, Scheffe). After crushing the optic nerve the BAX/Bcl-2 ratio was higher in the optic nerves and retina, application of P7C3-A20 significantly reduced this ratio. P7C3-A20 significantly increased the NAD level in the untouched optic nerves from 1.36 ± 0.05 to 1.59 ± 0.10 nmol/mg protein (P = 0.02, t test). Crushing the optic nerve decreased the level to 1.27 ± 0.21 nmol/mg protein and P7C3-A20 preserved the level at 1.43 ± 0.10 nmol/mg protein. Crushing the optic nerve decreased the mRNA levels of Nampt and Sirt-1 in the optic nerves, while P7C3-A20 significantly restored the levels.

Conclusions

P7C3-A20 can protect RGCs from optic nerve crushing possibly through preserving the NAD levels in the optic nerves.

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Acknowledgements

The authors thank Professor Duco Hamasaki, Bascom Palmer Eye Institute, University of Miami School of Medicine, for discussions and editing this manuscript.

Funding was provided by Grant-in-Aid for Scientific Research (KAKENHI) (Grant No. 16K11336).

Conflicts of interest

H. Oku, None; S. Morishita, None; T. Horie, None; Y. Nishikawa, None; T. Kida, None; M. Mimura, None; S. Kojima, None; T. Ikeda, None.

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Authors and Affiliations

  1. Department of Ophthalmology, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka, 569-8686, Japan

    Hidehiro Oku, Seita Morishita, Taeko Horie, Yuko Nishikawa, Teruyo Kida, Masashi Mimura, Shota Kojima & Tsunehiko Ikeda

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  1. Hidehiro Oku
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Correspondence to Hidehiro Oku.

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Oku, H., Morishita, S., Horie, T. et al. Protective effect of P7C3 on retinal ganglion cells from optic nerve injury. Jpn J Ophthalmol 61, 195–203 (2017). https://doi.org/10.1007/s10384-016-0493-6

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  • DOI: https://doi.org/10.1007/s10384-016-0493-6

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