Simvastatin upregulates Bcl-2 expression and protects retinal neurons from early ischemia/reperfusion injury in the rat retina

Simvastatin has been shown to enhance the survival of retinal ganglion cells (RGCs) following ischemia-reperfusion (IR) injury by mediating the expression of stress proteins. The purpose of this study was to investigate the effect of simvastatin on retinal neurons and the expression of apoptotic pro...

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Bibliographic Details
Published in:Experimental eye research 2011-11, Vol.93 (5), p.580-585
Main Authors: Ko, Mei-Lan, Chen, Chau-Fong, Peng, Pai-Huei, Peng, Yi-Hao
Format: Article
Language:English
Subjects:
Animal models
Animals
Antibodies
Apoptosis
Apoptosis - drug effects
Bax
Bax protein
Bcl-2
Bcl-2 protein
bcl-2-Associated X Protein - metabolism
Blotting, Western
Cell Count
Cell survival
Cell Survival - drug effects
Disease Models, Animal
Eye
Female
Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
In Situ Nick-End Labeling
Injuries
Intravitreal Injections
Ischemia
ischemia/reperfusion
Neurons
Neuroprotective Agents - administration & dosage
Neuroprotective Agents - pharmacology
Pressure
Proto-Oncogene Proteins c-bcl-2 - metabolism
Rats
Rats, Wistar
Reperfusion
Reperfusion Injury - metabolism
Reperfusion Injury - prevention & control
Retina
Retinal Diseases - metabolism
Retinal Diseases - prevention & control
retinal ganglion cell
Retinal ganglion cells
Retinal Ganglion Cells - drug effects
Retinal Ganglion Cells - metabolism
Simvastatin
Simvastatin - administration & dosage
Simvastatin - pharmacology
Stilbamidines - metabolism
stress proteins
Up-Regulation
Western blotting
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Summary:Simvastatin has been shown to enhance the survival of retinal ganglion cells (RGCs) following ischemia-reperfusion (IR) injury by mediating the expression of stress proteins. The purpose of this study was to investigate the effect of simvastatin on retinal neurons and the expression of apoptotic proteins in a rat IR model. Wistar rats received intravitreal injection of simvastatin immediately after retinal reperfusion. Retinal ischemia was induced by increasing intraocular pressure to 150mmHg for 60min. The number of viable RGCs was measured after retrograde labeling with Fluoro-Gold. Ischemia-induced apoptotic cell death was studied using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). We found that simvastatin treatment enhanced RGC survival after retinal ischemia by approximately 40% and decreased retinal neuronal apoptosis. Using western blot analysis, we found that simvastatin upregulated the expression of Bcl-2 in the retina. In contrast, the level of the protein Bax was unaffected by simvastatin treatment. Our results suggest that RGC loss induced by retinal IR may be prevented by simvastatin and that the mechanism underlying this process possibly involves an alteration in the apoptotic pathway. ► Simvastatin has been shown to enhance retinal ganglion cell (RGC) survival against ischemia-reperfusion (IR) injury. ► Simvastatin treatment increased RGC survival by proximately 40%. ► Simvastatin upregulated the expression of Bcl-2 in the retina as shown by western blot analysis. ► The expression of Bax was unaffected. ► The mechanism of simvastatin-mediated neuroprotection likely involves the apoptotic pathway.
ISSN:0014-4835
1096-0007
DOI:10.1016/j.exer.2011.07.003