June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Systemic symvastatin rescues death of retinal ganglion cells from optic nerve injury possibly through suppression of glial NF-κB activation
Author Affiliations & Notes
  • Seita Morishita
    Osaka Medical College, Takatsuki-shi, Japan
  • Hidehiro Oku
    Osaka Medical College, Takatsuki-shi, Japan
  • Masahiro Tonari
    Osaka Medical College, Takatsuki-shi, Japan
  • Teruyo Kida
    Osaka Medical College, Takatsuki-shi, Japan
  • Taeko Horie
    Osaka Medical College, Takatsuki-shi, Japan
  • Tsunehiko Ikeda
    Osaka Medical College, Takatsuki-shi, Japan
  • Footnotes
    Commercial Relationships Seita Morishita, None; Hidehiro Oku, None; Masahiro Tonari, None; Teruyo Kida, None; Taeko Horie, None; Tsunehiko Ikeda, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 114. doi:
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To determine whether systemic simvastatin rescues death of retinal ganglion cells (RGCs) from optic nerve injury.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: 629 optic nerve • 615 neuroprotection • 557 inflammation  
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