PMID- 21777583 OWN - NLM STAT- MEDLINE DCOM- 20120203 LR - 20131121 IS - 1096-0007 (Electronic) IS - 0014-4835 (Linking) VI - 93 IP - 5 DP - 2011 Nov TI - Simvastatin upregulates Bcl-2 expression and protects retinal neurons from early ischemia/reperfusion injury in the rat retina. PG - 580-5 LID - 10.1016/j.exer.2011.07.003 [doi] AB - 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. CI - Copyright (c) 2011 Elsevier Ltd. All rights reserved. FAU - Ko, Mei-Lan AU - Ko ML AD - Department of Ophthalmology, General Hsin-Chu Hospital, No. 25, Alley 442, Section One, Chin- Kuo Road, Hisnchu, Taiwan. aaddch@gmail.com FAU - Chen, Chau-Fong AU - Chen CF FAU - Peng, Pai-Huei AU - Peng PH FAU - Peng, Yi-Hao AU - Peng YH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110718 PL - England TA - Exp Eye Res JT - Experimental eye research JID - 0370707 RN - 0 (2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt) RN - 0 (Bax protein, rat) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 0 (Neuroprotective Agents) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Stilbamidines) RN - 0 (bcl-2-Associated X Protein) RN - AGG2FN16EV (Simvastatin) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Blotting, Western MH - Cell Count MH - Cell Survival/drug effects MH - Disease Models, Animal MH - Female MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage/*pharmacology MH - In Situ Nick-End Labeling MH - Intravitreal Injections MH - Neuroprotective Agents/administration & dosage/*pharmacology MH - Proto-Oncogene Proteins c-bcl-2/*metabolism MH - Rats MH - Rats, Wistar MH - Reperfusion Injury/metabolism/*prevention & control MH - Retinal Diseases/metabolism/*prevention & control MH - Retinal Ganglion Cells/*drug effects/metabolism MH - Simvastatin/administration & dosage/*pharmacology MH - Stilbamidines/metabolism MH - Up-Regulation MH - bcl-2-Associated X Protein/metabolism EDAT- 2011/07/23 06:00 MHDA- 2012/02/04 06:00 CRDT- 2011/07/23 06:00 PHST- 2011/01/10 00:00 [received] PHST- 2011/04/23 00:00 [revised] PHST- 2011/07/06 00:00 [accepted] PHST- 2011/07/23 06:00 [entrez] PHST- 2011/07/23 06:00 [pubmed] PHST- 2012/02/04 06:00 [medline] AID - S0014-4835(11)00216-8 [pii] AID - 10.1016/j.exer.2011.07.003 [doi] PST - ppublish SO - Exp Eye Res. 2011 Nov;93(5):580-5. doi: 10.1016/j.exer.2011.07.003. Epub 2011 Jul 18.