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

Abstract

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 150 mm Hg for 60 min. 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.

• Authors: Mei-Lan Ko, Chau-Fong Chen, Pai-Huei Peng, Yi-Hao Peng
• Journal: Experimental eye research (Exp Eye Res) Vol. 93 Issue 5 Pg. 580-5 (Nov 2011) ISSN: 1096-0007 [Electronic] England
• PMID: 21777583 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• 2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt
• Bax protein, rat
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Neuroprotective Agents
• Proto-Oncogene Proteins c-bcl-2
• Stilbamidines
• bcl-2-Associated X Protein
• Simvastatin

Topics

• Animals
• Apoptosis (drug effects)
• Blotting, Western
• Cell Count
• Cell Survival (drug effects)
• Disease Models, Animal
• Female
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (administration & dosage, pharmacology)
• In Situ Nick-End Labeling
• Intravitreal Injections
• Neuroprotective Agents (administration & dosage, pharmacology)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rats
• Rats, Wistar
• Reperfusion Injury (metabolism, prevention & control)
• Retinal Diseases (metabolism, prevention & control)
• Retinal Ganglion Cells (drug effects, metabolism)
• Simvastatin (administration & dosage, pharmacology)
• Stilbamidines (metabolism)
• Up-Regulation
• bcl-2-Associated X Protein (metabolism)