Epigenetic regulation of αA-crystallin in high myopia-induced dark nuclear cataract.
Epigenetic regulation of αA-crystallin in high myopia-induced dark nuclear cataract.
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DOI：
10.1371/journal.pone.0081900
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lu Y
中科院分区：
文献类型：
--
作者：
Zhu XJ;Zhou P;Zhang KK;Yang J;Luo Y;Lu Y
目的：探讨高度近视患者早发性暗核的病因及其与αA晶体蛋白表观遗传调控的关系。我们回顾了2012年在我们中心接受白内障手术的患者的临床数据。晶状体上皮细胞样本是在撕囊过程中采集的，而年轻的晶状体上皮细胞是捐献的。根据晶状体混浊分类系统III(LOCS III)对白内障的类型和严重程度进行分级。通过对CRYAA启动子的CpG岛进行焦糖测序，分析了以下组的DNA甲基化情况：年龄相关性白内障(ARC)核色(NC)2-3；高度近视白内障(HMC)NC2-3；ARC NC5-6；HMC NC5-6；以及年轻晶状体分级Nc1。采用实时定量聚合酶链式反应、逆转录聚合酶链式反应和免疫组织化学方法检测CRYAA基因的表达。高度近视患者暗核检出的优势比为5.16(95%可信区间：3.98~6.69；P<；0.001)。HMC NC5-6组晶状体上皮细胞CRYAA启动子CpG岛的甲基化程度最高，但HMC NC2-3组和ARC NC2-3组之间差异无统计学意义。同样，HMC NC5-6组CRYAA的mRNA和蛋白水平显著低于ARC NC5-6组和高度近视对照组。高度近视是暗核的危险因素。高度近视患者CRYAA基因启动子中CpG岛的高甲基化导致CRYAA基因表达下调可能是导致暗核早发的原因。
To assess the etiology of early-onset dark nucleus in high-myopic patients and its relationship with the epigenetic regulation of αA-crystallin (CRYAA). We reviewed clinical data from patients who underwent cataract surgery at our center in 2012. Lens epithelial samples were collected during capsulorhexis, whereas young lens epithelium was donated. Cataract type and severity were graded according to the Lens Opacity Classification System III (LOCS III). DNA methylation was analyzed by pyrosequencing the CpG islands of the CRYAA promoter in the following groups: Age-Related Cataract (ARC) Nuclear Color (NC) 2–3; High-Myopic Cataract (HMC) NC2–3; ARC NC5–6; HMC NC5–6; and in young lenses graded NC1. We analyzed CRYAA expression by real-time polymerase chain reaction (PCR), reverse transcription PCR, and immunohistochemistry. The odds ratio of dark nucleus in high-myopic patients was 5.16 (95% confidence interval: 3.98–6.69; p<0.001). CpG islands in lens epithelial CRYAA promoter in the HMC NC5–6 Group exhibited the highest methylation of all the groups, but no statistically significant differences were evident between the HMC NC2–3 and ARC NC2–3 Groups. Likewise, CRYAA mRNA and protein levels in the HMC NC5–6 Group were significantly lower than the ARC NC5–6 Group and high-myopic controls. High myopia is a risk factor for dark nucleus. Downregulation of CRYAA via the hypermethylation of CpG islands in its promoter could underlie the earlier onset of dark nucleus in high-myopic patients.
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影响因子：
4.1
作者：
MicelliFerrari, T;Vendemiale, G;Cardia, L
通讯作者：
Cardia, L
影响因子：
4.4
作者：
Pan, Chen-Wei;Wong, Tien-Yin;Saw, Seang-Mei
通讯作者：
Saw, Seang-Mei
影响因子：
4.2
作者：
Cheng, LY;Azen, SP;Freeman, WR
通讯作者：
Freeman, WR
影响因子：
4.4
作者：
Hunter, Allan;Spechler, Paul A.;Dunaief, Joshua L.
通讯作者：
Dunaief, Joshua L.
影响因子：
2.9
作者：
Pontikis, CC;Cella, CV;Cooper, JD
通讯作者：
Cooper, JD