Exfoliation Syndrome

剥脱综合征
  • 文章类型: Journal Article
    探讨lncRNAm6A甲基化修饰在假性剥脱性青光眼(PXG)患者房水(AH)中的作用。选择2021年6月至2021年12月接受手术的开角PXG患者。选择年龄和性别匹配的年龄相关性白内障(ARC)患者作为对照。患者接受了详细的眼科检查。在手术期间提取0.05-0.1mlAH用于MeRIP-Seq和RNA-Seq。联合分析用于筛选具有差异m6A甲基化修饰和表达的lncRNAs。使用在线软件工具绘制lncRNA-miRNA-mRNA网络(ceRNA)。使用定量实时PCR确认lncRNA和mRNA的表达。在PXG组中鉴定了总共4151个lncRNA和4386个相关的m6A甲基化修饰峰。同样,在对照中检测到2490个lncRNAs和2595个相关的m6A甲基化修饰峰。与ARC组相比,PXG组有234个高甲基化和402个低甲基化的m6A峰,差异有统计学意义(|倍数变化(FC)|≥2,p<0.05)。生物信息学分析显示,这些差异甲基化的lncRNA富集在细胞外基质形成中,紧密粘合,TGF-β信号通路,AMPK信号通路,和MAPK信号通路。联合分析鉴定了10个同时具有差异m6A甲基化和表达的lncRNAs。其中,RT-qPCR证实ENST000000485383和ROCK1的表达在PXG组中下调。m6A甲基化修饰可能影响lncRNA的表达,并通过ceRNA网络参与PXG的发病机制。ENST000000485383-hsamiR592-ROCK1可能是进一步研究PXGm6A甲基化的潜在靶途径。
    To explore the role of lncRNA m6A methylation modification in aqueous humour (AH) of patients with pseudoexfoliation glaucoma (PXG). Patients with open-angle PXG under surgery from June 2021 to December 2021 were selected. Age- and gender-matched patients with age-related cataract (ARC) were chosen as control. Patients underwent detailed ophthalmic examinations. 0.05-0.1 ml AH were extracted during surgery for MeRIP-Seq and RNA-Seq. Joint analysis was used to screen lncRNAs with differential m6A methylation modification and expression. Online software tools were used to draw lncRNA-miRNA-mRNA network (ceRNA). Expression of lncRNAs and mRNAs was confirmed using quantitative real-time PCR. A total of 4151 lncRNAs and 4386 associated m6A methylation modified peaks were identified in the PXG group. Similarly, 2490 lncRNAs and 2595 associated m6A methylation modified peaks were detected in the control. Compared to the ARC group, the PXG group had 234 hypermethylated and 402 hypomethylated m6A peaks, with statistically significant differences (| Fold Change (FC) |≥2, p < 0.05). Bioinformatic analysis revealed that these differentially methylated lncRNA enriched in extracellular matrix formation, tight adhesion, TGF- β signalling pathway, AMPK signalling pathway, and MAPK signalling pathway. Joint analysis identified 10 lncRNAs with differential m6A methylation and expression simultaneously. Among them, the expression of ENST000000485383 and ROCK1 were confirmed downregulated in the PXG group by RT-qPCR. m6A methylation modification may affect the expression of lncRNA and participate in the pathogenesis of PXG through the ceRNA network. ENST000000485383-hsa miR592-ROCK1 May be a potential target pathway for further investigation in PXG m6A methylation.
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  • 文章类型: Journal Article
    假性剥脱综合征(PEX)的特征是纤维性假性剥脱物质(PEXM)在眼睛中沉积,与该综合征相关的继发性青光眼具有更快和更严重的临床病程。PEX和假性剥脱性青光眼(PEXG)的发病率表现出种族聚集;然而,在亚洲人群中很少进行与PEX和PEXG相关的蛋白质组学研究。因此,我们旨在对维吾尔族白内障患者的房水(AH)进行蛋白质组学分析,患有PEX和白内障的人,以及患有PEXG和白内障的患者,以更好地了解疾病的分子机制并确定其潜在的生物标志物。为此,AH从白内障患者(n=10,对照组)收集,PEX伴白内障(n=10,PEX组),和PEXG白内障(n=10,PEXG组)在白内障超声乳化术中。使用无标记定量蛋白质组学技术结合生物信息学来鉴定和分析PEX和PEXG组的AH中的差异表达蛋白(DEP)。然后,收集独立的AH样本(每组12份),通过酶联免疫吸附试验(ELISA)验证DEP.PEX组展示了25个DEP,而PEXG组显示了44个DEP,与对照组相比。随后,我们在PEX和PEXG组中发现了三种新鉴定的蛋白质,其中FRAS1相关的细胞外基质蛋白2(FREM2)和破骨细胞相关受体(OSCAR)表现出下调,而凝血因子IX(F9)显示上调。生物信息学分析表明,细胞外基质相互作用,异常的血液衍生蛋白质,溶酶体主要参与PEX和PEXG的过程,PPI网络进一步显示F9可能是PEX和PEXG的潜在生物标志物。总之,本研究为理解PEX和PEXG中AH的蛋白质组学提供了新的信息。
    Pseudoexfoliation syndrome (PEX) is characterized by the deposition of fibrous pseudoexfoliation material (PEXM) in the eye, and secondary glaucoma associated with this syndrome has a faster and more severe clinical course. The incidence of PEX and pseudoexfoliative glaucoma (PEXG) exhibits ethnic clustering; however, few proteomic studies related to PEX and PEXG have been conducted in Asian populations. Therefore, we aimed to conduct proteomic analysis on the aqueous humor (AH) obtained from Uyghur patients with cataracts, those with PEX and cataracts, and those with PEXG and cataracts to better understand the molecular mechanisms of the disease and identify its potential biomarkers. To this end, AH was collected from patients with cataracts (n = 10, control group), PEX with cataracts (n = 10, PEX group), and PEXG with cataracts (n = 10, PEXG group) during phacoemulsification. Label-free quantitative proteomic techniques combined with bioinformatics were used to identify and analyze differentially expressed proteins (DEPs) in the AH of PEX and PEXG groups. Then, independent AH samples (n = 12, each group) were collected to validate DEPs by enzyme-linked immunosorbent assay (ELISA). The PEX group exhibited 25 DEPs, while the PEXG group showed 44 DEPs, both compared to the control group. Subsequently, we found three newly identified proteins in both PEX and PEXG groups, wherein FRAS1-related extracellular matrix protein 2 (FREM2) and osteoclast-associated receptor (OSCAR) exhibited downregulation, whereas coagulation Factor IX (F9) displayed upregulation. Bioinformatics analysis suggested that extracellular matrix interactions, abnormal blood-derived proteins, and lysosomes were mainly involved in the process of PEX and PEXG, and the PPI network further revealed F9 may serve as a potential biomarker for both PEX and PEXG. In conclusion, this study provides new information for understanding the proteomics of AH in PEX and PEXG.
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  • 文章类型: Journal Article
    背景:假性剥脱(XFS)是当今青光眼的常见原因。由于XFS导致继发性青光眼(XFG)的不可逆失明,本研究旨在确定中国新疆XFS的患病率,并确定XFS中涉及的hub基因。
    方法:从2007年至2019年,对50岁及以上的患者进行了回顾性图表回顾。所有通过裂隙灯检查诊断为XFS或XFG的患者均通过图表审查进行鉴定。
    结果:在可查看的84例患者图表中,50%的患者是男性,平均年龄67岁。确定了PPI网络中通过连通性程度评估的前10个基因。结果显示Tyrobp是最优秀的基因,其次是Ptprc,Fcgr3,Itgb2,Emr1,Cd68,Syk,Fcerlg,Hck,Lyz2所有这些hub基因在XFS中下调。
    结论:我们的发现显示了XFS在诊断和治疗中的重要生物标志物。
    BACKGROUND: Pseudoexfoliation (XFS) is a common cause of glaucoma in nowadays. Because of XFS causing irreversible blindness secondary to glaucoma (XFG), this study aims to identify the current prevalence of XFS among Xinjiang Province of China, and identify the hub genes involved in XFS.
    METHODS: A retrospective chart review was conducted from 2007 to 2019 for patients aged 50 and older. All patients with XFS or XFG diagnosed by slit lamp exam were identified through chart review.
    RESULTS: Of the 84 patient charts available for review, 50% of the patients identified as male, with a mean age of 67 years. The top ten genes evaluated by connectivity degree in the PPI network were identified. The results showed that Tyrobp was the most outstanding gene, followed by Ptprc, Fcgr3, Itgb2, Emr1, Cd68, Syk, Fcerlg, Hck, and Lyz2. All of these hub genes were downregulated in XFS.
    CONCLUSIONS: Our findings show a considerably biomarkers of XFS for diagnosis and treatment.
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  • 文章类型: Journal Article
    目的:本研究旨在研究剥脱综合征(XFS)和剥脱性青光眼(XFG)患者的眼前节参数。
    方法:本研究采用回顾性病例系列设计,共有56例(112只眼)与XFS/XFG无关(XFS:26例/60只眼;XFG:30例/44只眼)和100例年龄相关性白内障病例作为对照组(200只眼)。参与者在新疆医科大学第一附属医院眼科进行评估。临床数据,包括眼轴长度,前房深度,白到白的距离,中央角膜厚度,和角膜内皮细胞密度(ECD),收集进行统计分析。
    结果:ECD在XFS/XFG和年龄相关性白内障组之间表现出显著差异(P<0.001),其余指标差异无统计学意义(P>0.05)。XFS和XFG患者的眼部参数与年龄相关性白内障患者的眼部参数不同,结果一致。值得注意的是,XFS和XFG患者之间无统计学差异。
    结论:与年龄相关性白内障受试者相比,XFS/XFG患者的ECD降低。保持警惕以提高XFS/XFG患者的手术安全性并积极预防并发症至关重要。
    OBJECTIVE: This study aimed to investigate anterior segment parameters in patients with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG).
    METHODS: The study adopted a retrospective case series design, involving a total of 56 patients (112 eyes) with unrelated XFS/XFG (XFS: 26 patients/60 eyes; XFG: 30 patients/44 eyes) and 100 age-related cataract cases as the control group (200 eyes). The participants were evaluated at the ophthalmology department of the First Affiliated Hospital of Xinjiang Medical University. Clinical data, including eye axial length, anterior chamber depth, white-to-white distance, central corneal thickness, and corneal endothelial cell density (ECD), were collected for statistical analysis.
    RESULTS: ECD exhibited a significant difference between the XFS/XFG and age-related cataract groups (P < 0.001), while the remaining indexes did not show statistical differences (P > 0.05). Ocular parameters in patients with XFS and XFG were distinct from those in age-related cataract cases, with consistent results. Notably, there were no statistically significant differences between XFS and XFG patients.
    CONCLUSIONS: ECD is reduced in XFS/XFG patients compared with age-related cataract subjects. It is crucial to remain vigilant to enhance surgical safety in XFS/XFG patients and prevent complications proactively.
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  • 文章类型: Journal Article
    调查在欧洲人群中使用阳光/紫外线(UV)防护和皮肤晒黑的便利性与假性剥脱性青光眼(PXG)风险之间的潜在因果关系。
    从由498,751名欧洲参与者组成的UKBiobank全基因组关联研究数据库中选择与使用防晒/紫外线防护和皮肤晒黑容易相关的单核苷酸多态性(SNP)。PXG的SNP来自FinnGen研究,包括3424例PXG病例和326,434例对照。进行了两个样本孟德尔随机化(MR)分析,以评估使用阳光/紫外线防护和皮肤晒黑的便利性与PXG风险之间的关联。
    遗传易感性的逆方差加权回归预测,在欧洲祖先中,使用阳光/紫外线防护和皮肤晒黑的容易度与PXG风险降低潜在正相关(使用阳光/紫外线防护:比值比[OR]=0.47;95%置信区间[CI],0.24-0.92;P=0.028;皮肤晒黑的容易程度:OR=0.81;95%CI,0.67-0.97;P=0.025)。
    我们发现遗传证据支持欧洲人群中紫外线防护和降低PXG风险之间的潜在因果关系。进一步的研究将有助于阐明潜在的机制,并促进对眼睛的紫外线保护,特别是在PXG风险较高的人群中。
    To investigate the potential causal associations between the use of sun/ultraviolet (UV) protection and ease of skin tanning and the risk of pseudoexfoliation glaucoma (PXG) in European populations.
    Single nucleotide polymorphisms (SNPs) associated with the use of sun/UV protection and ease of skin tanning were selected from the UK Biobank genome-wide association study database consisting of 498,751 European participants. SNPs of PXG were obtained from the FinnGen study including 3424 PXG cases and 326,434 controls. Two-sample Mendelian randomization (MR) analyses were performed to assess the association between the use of sun/UV protection and ease of skin tanning and risk of PXG.
    Inverse variance weighted regression of genetic susceptibility predicted that both use of sun/UV protection and ease of skin tanning were potentially positively associated with the decreased risk of PXG in the European ancestry (use of sun/UV protection: odds ratio [OR] = 0.47; 95% confidence interval [CI], 0.24-0.92; P = 0.028; ease of skin tanning: OR = 0.81; 95% CI, 0.67-0.97; P = 0.025).
    We found genetic evidence supporting a potential causal association between UV protection and a decreased risk of PXG in European population. Further research will help elucidate the underlying mechanisms and promote UV protection for eyes, especially in people with a high risk of PXG.
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  • 文章类型: Review
    背景:MRCS(微角膜,视网膜营养不良,白内障,和后部葡萄肿)综合征和极长轴很少见,因为微角膜经常伴随着整个眼前节的缩小,偶尔伴随着整个眼球的缩小。在这里介绍的案例中,确定了这两个元素的组合,连同XFS(剥脱综合征)。
    方法:一名66岁的汉族妇女因视力受损而就诊,该视力在她的整个一生中都伴随着视力受损,并在过去两年中恶化。两眼均明确诊断为MRCS综合征和极长眼轴。她的右眼确认了XFS,但是突变筛查未能在先前报道的一些特定基因中识别出致病序列变异,包括BEST1和ARL2。然而,确定了FBN2基因中可能的致病突变。使用巩膜隧道切口并在全身麻醉下进行双侧白内障超声乳化术,不进行人工晶状体植入。在3个月的随访中,患者的眼部恢复令人满意。
    结论:这里介绍的病例表现出罕见的MRCS综合征共存,极长的轴和XFS。她眼部异常的复杂性给手术管理带来了挑战,通常需要多学科合作。此外,这种情况下的遗传分析产生了MRCS综合征可能的新候选基因,并提供了支持该表型遗传异质性的证据.
    BACKGROUND: The coexistence of MRCS (microcornea, retinal dystrophy, cataract, and posterior staphyloma) syndrome and extremely long axis is rare since microcornea frequently accompanies with diminution of entire anterior segment and occasionally the whole globe. In the case presented here, combination of these two elements were identified, together with XFS (exfoliation syndrome).
    METHODS: A 66-year-old Han Chinese woman presented for consultation due to impaired vision which accompanied throughout her entire life span and worsened during the last 2 years. Combination of MRCS syndrome and extremely long axial length was evidently diagnosed in both eyes, with XFS confirmed in her right eye, but mutation screening failed to identify disease-causing sequence variants in some specific genes reported previously, including BEST1 and ARL2. However, likely pathogenic mutations in FBN2 gene were identified. Bilateral cataract phacoemulsification without intraocular lens implantation was performed using scleral tunnel incision and under general anesthesia. At 3-month follow-up, ocular recovery of the patient was satisfactory.
    CONCLUSIONS: The case presented here exhibited rare coexistence of MRCS syndrome, extremely long axis and XFS. The complexity of her ocular abnormalities brought challenges to surgical management, in which multidisciplinary collaboration is often required. Furthermore, the genetic analysis in this case yielded a possible novel candidate gene for MRCS syndrome and provided evidence in support of genetic heterogeneity in this phenotype.
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  • 文章类型: Journal Article
    N6-甲基腺苷(m6A)修饰是真核mRNA中最常见的甲基化修饰类型之一。然而,其在假性剥脱性青光眼(PXG)发病机制中的作用尚未见报道。为了加强这方面的认识,我们评估了PXG患者房水中的m6A甲基化体。进行了MeRIP-Seq和RNA-Seq分析,以比较PXG患者与年龄相关性白内障(ARC)患者房水的m6A甲基化组和基因表达谱。进行比色m6A定量以检测全局m6A水平。定量逆转录PCR证实了两组中m6A相关酶和mRNA的表达。结果显示,PXG组的房水m6A水平明显高于ARC组。五种m6A相关酶,包括METTL3,YTHDC2,HNRNPA2B1,HNRNPC,和LRPPRC,在PXG标本中显著上调。我们还在PXG组中观察到与6126个基因转录本相关的9728个m6A修饰的峰,超过250个基因含有一个m6A峰(低甲基化或高甲基化)。m6A峰的分布在两个组的编码序列和3'-非翻译区中富集。GGAC基序结构也显著富集。生物信息学分析进一步表明,m6A在细胞外基质形成和组蛋白脱乙酰化中起关键作用。此外,MMP14、ADAMTSL1、FN1和HDAC1在PXG组中显示m6A甲基化和mRNA表达的显著转变。因此,m6A甲基化可以调节PXG中的细胞外基质组成,METTL3可能是该过程的关键调节因子。在未来,有必要研究潜在的靶基因MMP14,ADAMTSL1,FN1和HDAC1.
    N6-methyladenosine (m6A) modification is one of the most common types of methylation modifications in eukaryotic mRNA. However, its role in the pathogenesis of pseudoexfoliation glaucoma (PXG) has not yet been reported. To enhance understanding in this regard, we assessed the m6A methylome in the aqueous humor of patients with PXG. MeRIP-Seq and RNA-Seq analyses were performed to compare the m6A methylomes and gene expression profiles of the aqueous humor of patients with PXG with those of patients with age-related cataract (ARC). Colorimetric m6A quantification was performed to detect global m6A levels. Quantitative reverse transcription PCR confirmed the expression of m6A-related enzymes and mRNAs in both groups. Results showed significantly higher aqueous humor m6A levels in the PXG group than in the ARC group. Five m6A-related enzymes, including METTL3, YTHDC2, HNRNPA2B1, HNRNPC, and LRPPRC, were significantly up-regulated in PXG specimens. We also observed 9728 m6A-modified peaks related to 6126 gene transcripts in the PXG group, with more than 250 genes containing one m6A peak (hypomethylated or hypermethylated). The distribution of the m6A peaks was enriched in coding sequences and 3\'-untranslated regions for both groups. GGAC motif structures were also significantly enriched. Bioinformatics analysis further revealed that m6A plays a critical role in extracellular matrix formation and histone deacetylation. Additionally, MMP14, ADAMTSL1, FN1, and HDAC1 showed significant changes in m6A methylation and mRNA expression in the PXG group. Therefore, m6A methylation may regulate extracellular matrix composition in PXG and METTL3 may be a pivotal regulator of this process. In the future, it would be necessary to investigate MMP14, ADAMTSL1, FN1, and HDAC1, which are potential target genes.
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  • 文章类型: Journal Article
    背景:评估糖尿病患者瞳孔扩张后AAC和眼内压(IOP)变化的风险。
    方法:这项横断面研究纳入了广州市社区居民中2,287名糖尿病患者,中国。除非有青光眼病史,否则所有参与者均接受常规瞳孔扩张。在瞳孔扩张之前和之后一小时使用非接触式眼压计用0.5%的托吡卡胺和0.5%的去氧肾上腺素滴眼液测量IOP。评估瞳孔扩张后AAC的比例和眼压的变化。
    结果:2,287名糖尿病患者中只有一名(0.04%)出现了扩张后AAC。右侧扩张前后平均IOP为16.1±2.7和16.5±2.8mmHg(P<0.001);左侧扩张前后平均IOP为16.5±2.7和16.8±2.8mmHg(P<0.001)。61名参与者(2.7%)显示IOP升高≥5mmHg,25名参与者(1.1%)显示扩张后IOP>25mmHg,包括11名(0.5%)IOP升高≥5mmHg和扩张后IOP>25mmHg的参与者.在多变量逻辑回归分析中,较低的扩张前眼压(OR=0.827;95%CI,0.742-0.922;P=0.001)和较浅的前房深度(ACD)(OR=0.226;95%CI,0.088-0.585;P=0.002)是眼压升高≥5mmHg的重要危险因素。
    结论:糖尿病患者瞳孔扩张后发生AAC的风险非常低。较低的扩张前IOP和较浅的ACD是扩张后IOP增加的危险因素。
    To evaluate the risk of AAC and intraocular pressure (IOP) changes in diabetic patients after pupil dilation.
    This cross-sectional study enrolled 2,287 diabetic patients among community residents in Guangzhou, China. All participants underwent routine pupil dilation unless they had a history of glaucoma. IOP was measured using a non-contact tonometer before and one hour after pupil dilation with tropicamide 0.5% and phenylephrine 0.5% eye drop. The proportion of AAC and changes in IOP after pupil dilation were evaluated.
    Only one of the 2,287 participants (0.04%) with diabetes developed post-dilation AAC. The mean pre and post-dilation IOP in the right was 16.1 ± 2.7 and 16.5 ± 2.8 mmHg (P < 0.001); mean pre and post-dilation IOP in the left was 16.5 ± 2.7 and 16.8 ± 2.8 mmHg (P < 0.001). Sixty-one participants (2.7%) showed an increase in IOP ≥ 5 mmHg and 25 participants (1.1%) showed a post-dilation IOP > 25 mmHg, including 11 participants (0.5%) who had both an increase in IOP ≥ 5 mmHg and post-dilation IOP > 25 mmHg. Lower pre-dilation IOP (OR = 0.827; 95% CI, 0.742-0.922; P = 0.001) and shallower anterior chamber depth (ACD) (OR = 0.226; 95% CI, 0.088-0.585; P = 0.002) were significant risk factors for an increase in IOP ≥ 5 mmHg in multivariate logistic regression analysis.
    The risk of developing AAC after pupil dilation in diabetic patients was very low. Lower pre-dilation IOP and shallower ACD are risk factors for increased post-dilation IOP.
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  • 文章类型: English Abstract
    Exfoliative glaucoma is a type of glaucoma secondary to pseudoexfoliation syndrome. In recent years, great progress has been made in the research of pathogenesis and risk factors of exfoliative glaucoma. A variety of risk genes, abnormal growth factors and cytokines, changes in the anterior and posterior segments have been found. Based on the systematic summary of these achievements, this article points out the problems that need to be further studied, so as to provide a reference for future research in this field.
    剥脱性青光眼是继发于剥脱综合征的一种青光眼类型。近年来,国内外学者对剥脱性青光眼的发病机制和危险因素进行了大量研究,发现了多种危险基因、异常表达的生长因子和细胞因子以及广泛的眼前、后节改变。剥脱性青光眼与全身疾病和环境存在一定关联。本文在对这些成果进行系统总结的基础上,指出当前亟待进行深入研究的问题,以期为该领域提供参考。.
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  • 文章类型: Journal Article
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