Yang Jing, Zhou Sheng, Gu Jianjun, Wang Yujuan, Guo Minfei, Liu Yizhi
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Department of Ophthalmology, The First People's Hospital of Foshan, Guangdong, China.
PLoS One. 2015 Jun 19;10(6):e0130705. doi: 10.1371/journal.pone.0130705. eCollection 2015.
To investigate the activation of three unfolded protein response (UPR) pathways in the lenses of age-related, high myopia-related and congenital cataracts.
Lens specimens were collected from patients during small incision cataract surgery. Lenses from young cadaver eyes were collected as normal controls. Real-time PCR and Western blotting were performed to detect the expression of GRP78, p-eIF2α, spliced XBP1, ATF6, ATF4 and p-IRE1α in the lenses of normal human subjects and patients with age-related, myopia-related or congenital cataracts.
In the lenses of the age-related and high myopia-related cataract groups, the protein levels of ATF6, p-eIF2α and p-IRE1α and the gene expression levels of spliced XBP1, GRP78, ATF6 and ATF4 were greatly increased. Additionally, in the congenital cataract group, the protein levels of p-eIF2α and p-IRE1α and the gene expression levels of spliced XBP1, GRP78 and ATF4 were greatly increased. However, the protein and gene expression levels of ATF6 were not up-regulated in the congenital cataract group compared with the normal control group.
The UPR is activated via different pathways in the lenses of age-related, high myopia-related and congenital cataracts. UPR activation via distinct pathways might play important roles in cataractogenesis mechanisms in different types of cataracts.
研究年龄相关性、高度近视相关性和先天性白内障晶状体中三条未折叠蛋白反应（UPR）途径的激活情况。
在小切口白内障手术期间从患者处收集晶状体标本。收集年轻尸体眼的晶状体作为正常对照。采用实时聚合酶链反应（PCR）和蛋白质免疫印迹法检测正常人和年龄相关性、近视相关性或先天性白内障患者晶状体中葡萄糖调节蛋白78（GRP78）、磷酸化真核翻译起始因子2α（p-eIF2α）、剪接型X盒结合蛋白1（spliced XBP1）、活化转录因子6（ATF6）、活化转录因子4（ATF4）和磷酸化肌醇需求酶1α（p-IRE1α）的表达。
在年龄相关性和高度近视相关性白内障组晶状体中，ATF6、p-eIF2α和p-IRE1α的蛋白水平以及spliced XBP1、GRP78、ATF6和ATF4的基因表达水平显著升高。此外，在先天性白内障组中，p-eIF2α和p-IRE1α的蛋白水平以及spliced XBP1、GRP78和ATF4的基因表达水平显著升高。然而，与正常对照组相比，先天性白内障组中ATF6的蛋白和基因表达水平未上调。
年龄相关性、高度近视相关性和先天性白内障晶状体中UPR通过不同途径被激活。通过不同途径激活的UPR可能在不同类型白内障的发病机制中起重要作用。
