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- Title
Protective effect of P7C3 on retinal ganglion cells from optic nerve injury.
- Authors
Oku, Hidehiro; Morishita, Seita; Horie, Taeko; Nishikawa, Yuko; Kida, Teruyo; Mimura, Masashi; Kojima, Shota; Ikeda, Tsunehiko
- 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/mm in the sham controls; it was significantly lower in the crush-placebo group at 979.7 ± 144.3 cells/mm ( P < 0.0001). The neuroprotective effects of P7C3-A20 was demonstrated by the significantly higher density of 1266.0 ± 193.1 cells/mm 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.
- Subjects
RETINAL ganglion cells; NEUROPROTECTIVE agents; OPTIC nerve injuries; MESSENGER RNA; NAD (Coenzyme)
- Publication
Japanese Journal of Ophthalmology, 2017, Vol 61, Issue 2, p195
- ISSN
0021-5155
- Publication type
Article
- DOI
10.1007/s10384-016-0493-6