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Seita Morishita, Hidehiro Oku, Masahiro Tonari, Teruyo Kida, Taeko Horie, Tsunehiko Ikeda; Systemic symvastatin rescues death of retinal ganglion cells from optic nerve injury possibly through suppression of glial NF-κB activation. Invest. Ophthalmol. Vis. Sci. 2013;54(15):114.
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To determine whether systemic simvastatin rescues death of retinal ganglion cells (RGCs) from optic nerve injury.
We studied the effect of systemic simvastatin on the survival of RGCs after the optic nerve of rats was crushed. Simvastatin (3.0 mg/kg/day) or its solvent (placebo) was given through an osmotic mini-pump 1week prior to crushing the optic nerves. We also performed immunohistological evaluations and real-time PCR to determine the expressions of the CD68, TNF-α, and iNOS genes in the neuroinflammation of the crushed optic nerves.
There was a recruitment of CD68 positive cells, namely microglia/macrophages, at the crushed site. Assessment by real time PCR showed that mRNA levels of CD68 significantly increased after crushing the optic nerve, which peaked on day 5. Systemic simvastatin significantly (P=0.002, ANOVA followed by Fisher) suppressed the increase on day 3. In addition, simvastatin significantly suppressed up-regulation of TNF-α and iNOS genes. The mean number (± SEM) of RGCs stained by TUJ-1 antibody was 1816.3 ± 94.9/mm2 in sham operated rats (n=6), which decreased to 831.4 ± 82.6/mm2 (n = 9) on day 7 after the optic nerve was crushed with placebo treatment. This reduction was significantly (P=0.01, Scheffe) reduced to 1169.2 ± 82.2/mm2 (n = 9) with systemic simvastatin treatment. We also found simvastatin (1.0 μM) significantly suppressed NF-κB activation and iNOS expression caused by TNF-α (50ng/ml) in cultured optic nerve astrocytes.
These results suggested that systemic simvastatin suppressed the neuro-inflammtion and rescued death of RGCs after crushing the optic nerves. One possible mechanism of the neuro-protective role is suppression of NF-κB activation of optic nerve astrocytes.
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