Tawfik Amany, Smith Sylvia B
Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University, Augusta, GA ; James and Jean Culver Vision Discovery Institute, Georgia Regents University, Augusta, GA.
Department of Cellular Biology and Anatomy, Medical College of Georgia, Georgia Regents University, Augusta, GA ; James and Jean Culver Vision Discovery Institute, Georgia Regents University, Augusta, GA ; Department of Ophthalmology, Medical College of Georgia, Georgia Regents University, Augusta, GA.
Austin J Clin Ophthalmol. 2014 Jun 16;1(5):1023.
Hyperhomocysteinemia is implicated in retinal neurovascular diseases including arterial occlusive disease, venous occlusive disease and pseudoexfoliation glaucoma. The mechanism for these diseases is not known. Here we used hyperhomocysteinemic mice lacking the gene encoding cystathionine-beta-synthase () to examine whether ER stress could be a mechanism for the retinal neurovasculopathy reported in these mice. Retinas of and mice (age: 3-5 wks) were used to investigate the expression of ER stress genes () and the proteins they encode. The levels of poly(ADP-ribose) polymerase (PARP) and cleaved ysteine-artic prote (caspase-3), proteins known to be involved in apoptosis, were also examined. Quantitative reverse transcription polymerase chain reaction and western blotting revealed an increase in BiP/GRP78 and PERK in retinas of mice compared with mice. There was an elevation of CCAAT-enhancer-binding protein homologous protein (CHOP) in retinal cryosections of mice indicating apoptosis, which was confirmed by increased levels of PARP and cleaved caspase-3. The data suggest that the genes and proteins that are major players in the ER stress pathway, particularly the PERK pathway, are upregulated in retinas of mice. The data support a role for ER stress in the pathophysiology associated with the hyperhomocysteinemia-linked retinal disease.
高同型半胱氨酸血症与包括动脉闭塞性疾病、静脉闭塞性疾病和假性剥脱性青光眼在内的视网膜神经血管疾病有关。这些疾病的发病机制尚不清楚。在此，我们使用缺乏编码胱硫醚-β-合酶（）基因的高同型半胱氨酸血症小鼠，来研究内质网应激是否可能是这些小鼠视网膜神经血管病变的一种机制。使用和小鼠（年龄：3 - 5周）的视网膜来研究内质网应激基因（）及其编码蛋白的表达。还检测了已知参与细胞凋亡的聚（ADP - 核糖）聚合酶（PARP）和裂解的半胱天冬酶 - 3（caspase - 3）的水平。定量逆转录聚合酶链反应和蛋白质印迹分析显示，与小鼠相比，小鼠视网膜中结合免疫球蛋白蛋白（BiP）/葡萄糖调节蛋白78（GRP78）和蛋白激酶R样内质网激酶（PERK）增加。小鼠视网膜冰冻切片中CCAAT增强子结合蛋白同源蛋白（CHOP）升高，表明存在细胞凋亡，PARP和裂解的caspase - 3水平升高证实了这一点。数据表明，内质网应激途径中的主要基因和蛋白，特别是PERK途径，在小鼠视网膜中上调。这些数据支持内质网应激在与高同型半胱氨酸血症相关的视网膜疾病的病理生理学中发挥作用。
