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Hidehiro Oku, Taeko Horie, Teruyo Kida, Tsunehiko Ikeda; P7C3 Suppresses Neuroinflammation and Protects Retinal Ganglion Cells of Rats from Optic Nerve Crush.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2485. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To determine whether P7C3-A20 can inhibit the phosphorylation of the mammalian target of rapamycin (mTOR), depress neuroinflammation, and protect retinal ganglion cells (RGCs) of rats from optic nerve crush (ONC).
The left optic nerve was crushed, and 5.0 mg/kg/d of P7C3-A20, 1.0 mg/kg/d of rapamycin, or their vehicle was injected intraperitoneally beginning 1 day before the ONC. The protective effects on the RGCs were determined by immunohistochemical staining for Tuj-1. The level of phosphorylated mTOR was determined by immunoblotting. The neuroinflammation in the optic nerve was determined by changes in the expression of CD68, TNF-a, MCP-1, and iNOS.
The density of Tuj-1–stained cells in the control was 2010.6±81.5/mm2 on days 7 after the sham operation (n=6). The level was lower at 995 6±122/mm2 on day 7 after the ONC (n=8). Rapamycin and P7C3-A20 preserved the density at significantly higher levels at 1432. 6±120 /mm2 (n=6) and 1393.6±149/mm2 (n=6), respectively (P < 0.05, Scheffe test). The ONC caused 1.56-fold incarese of phosphorylated mTOR level in the optic nerve above the control level on day 7. Rapamycin and P7C3 significantly lowered the level of phosphorylated mTOR to 0.89-fold and 0.67-fold of the control, respectively. There was an accumulation of CD68 positive cells that were immunoreactive to TNF-a at the crush site. The expression of MCP-1 and iNOS was increased chiefly in the astrocytes around the lesion. These inflammatory events were suppressed by both rapamycin and P7C3.
P7C3-A20 can inhibit mTOR phosphorylation in the crushed optic nerve, which may suppress neuroinflammation and preserve the RGCs.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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