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

被引:39
作者
Ko, Mei-Lan [2 ,3 ]
Chen, Chau-Fong [4 ]
Peng, Pai-Huei [1 ,5 ]
Peng, Yi-Hao [6 ]
机构
[1] Shin Kong Wu Ho Su Mem Hosp, Dept Ophthalmol, Taipei, Taiwan
[2] Gen Hsin Chu Hosp, Dept Ophthalmol, Hisnchu, Taiwan
[3] Natl Tsing Hua Univ, Dept Biomed Engn & Environm Sci, Hsinchu, Taiwan
[4] Natl Taiwan Univ, Coll Med, Dept Physiol, Taipei 10764, Taiwan
[5] Fu Jen Catholic Univ, Coll Med, New Taipei, Taiwan
[6] China Med Univ Hosp, Dept Resp Therapy, Div Pulm & Crit Care Med, Taichung 404, Taiwan
关键词
retinal ganglion cell; simvastatin; Bcl-2; Bax; ischemia/reperfusion; ISCHEMIA-REPERFUSION INJURY; PROGRAMMED CELL-DEATH; GANGLION-CELLS; IN-VIVO; APOPTOSIS; BAX; STATINS; NEUROPROTECTION; DAMAGE; GLAUCOMA;
D O I
10.1016/j.exer.2011.07.003
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
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 mmHg 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. (C) 2011 Elsevier Ltd. All rights reserved.
引用
收藏
页码:580 / 585
页数:6
相关论文
共 37 条
[11]   Pitavastatin: Protection against neuronal retinal damage induced by ischemia-reperfusion injury in rats [J].
Kawaji, Takahiro ;
Inomata, Yasuya ;
Takano, Alkiomi ;
Sagara, Nina ;
Inatani, Masaru ;
Fukushima, Mikiko ;
Tanihara, Hidenobu .
CURRENT EYE RESEARCH, 2007, 32 (11) :991-997
[12]   Simvastatin promotes heat shock protein 27 expression and Akt activation in the rat retina and protects axotomized retinal ganglion cells in vivo [J].
Kretz, A ;
Schmeer, C ;
Tausch, S ;
Isenmann, S .
NEUROBIOLOGY OF DISEASE, 2006, 21 (02) :421-430
[13]  
Kwak B, 2001, SWISS MED WKLY, V131, P41
[14]   Alpha-2 adrenoceptor agonist protects retinal function after acute retinal ischemic injury in the rat [J].
Lai, RK ;
Chun, T ;
Hasson, D ;
Lee, S ;
Mehrbod, F ;
Wheeler, L .
VISUAL NEUROSCIENCE, 2002, 19 (02) :175-185
[15]  
Lam TT, 1999, INVEST OPHTH VIS SCI, V40, P967
[16]   Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics [J].
Letai, A ;
Bassik, MC ;
Walensky, LD ;
Sorcinelli, MD ;
Weiler, S ;
Korsmeyer, SJ .
CANCER CELL, 2002, 2 (03) :183-192
[17]   Simvastatin and Disease Stabilization in Normal Tension Glaucoma: A Cohort Study [J].
Leung, Dexter Y. L. ;
Li, Felix C. H. ;
Kwong, Yolanda Y. Y. ;
Tham, Clement C. Y. ;
Chi, Stanley C. C. ;
Lam, Dennis S. C. .
OPHTHALMOLOGY, 2010, 117 (03) :471-476
[18]   Statins and other cholesterol-lowering medications and the presence of glaucoma [J].
McGwin, G ;
McNeal, S ;
Owsley, C ;
Girkin, C ;
Epstein, D ;
Lee, PP .
ARCHIVES OF OPHTHALMOLOGY, 2004, 122 (06) :822-826
[19]   Statins -: a cure-all for the brain? [J].
Menge, T ;
Hartung, HP ;
Stüve, O .
NATURE REVIEWS NEUROSCIENCE, 2005, 6 (04) :325-331
[20]   Lovastatin inhibits TGF-β-induced myofibroblast transdifferentiation in human tenon fibroblasts [J].
Meyer-ter-Vehn, Tobias ;
Katzenberger, Barbara ;
Han, Hong ;
Grehn, Franz ;
Schlunck, Guenther .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2008, 49 (09) :3955-3960