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