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青光眼术后IL6和PRG4基因型与结膜纤维化的关系

Yu-Wai-Man, C., Tagalakis, A.D., Meng, J., et al.

期刊名称:JAMA Ophthalmology

卷期:2017年第135卷第11期

摘要

摘要:重要性:术后纤维化是青光眼手术获得长期成功的一个关键决定因素,目前还没有可靠的生物标志物来对瘢痕形成的风险进行分层。目的:旨在比较青光眼手术后候选基因表达纤维化组织生物标志物的结膜纤维化患者的临床表型。设计,设置和研究对象:这项横断面研究从201491日到201691日,在Moorfields眼科医院招募了进行青光眼手术的 42名患者。参与者分为纤维化组和无纤维化组。主要预后指标:IL6PRG4基因与详细的临床表型之间的基因型-表型相关性。使用原位免疫组织化学分析来评估结膜组织中的IL6PRG4蛋白表达。以151表示0; 2,25; 3,50; 4,75;5,100%)对中心泡区,最大泡区和泡区高度进行分级。 Bleb血管分级评分为1-5级(1级表示无血管,2级,正常,3级,轻度,4级,中度,5级,严重充血)结果:研究期间共招募42例患者(平均年龄43.8岁,女性3.6岁,女性16岁,女性57岁,白人22例,女性22例,占79%),和14例(33%)(平均[SD]年龄47.7 [6.9];女性4 [29];白人9 [64])以前没有接受过青光眼手术者(非纤维组)。纤维化组具有显着的瘢痕形成和血管形成以及较差的logMAR视力。平均(SD)分级为中心水泡面积1.40.1),水泡高度1.40.1),水泡血管性3.40.2)。与非纤维化细胞系(平均0.011)相比,IL6基因在纤维化细胞系中上调(平均0.040)(差异0.029; 95CI0.015-0.043; P = 0.003)。与非纤维化细胞系相比,PRG4基因在纤维化细胞系(0.002)中也下调(平均值0.109;差异0.107; 95CI 0.104-0.110; P = 0.03)。研究发现IL6基因与青光眼手术次数(r = 0.94P <0.001)和logMAR视力(r = 0.64P = 0.03)有很强的相关性。 PRG4基因与青光眼手术次数(r = -0.72P = .005)和logMAR视力(r = -0.62P = 0.03)呈中度相关。结论和相关性:IL6PRG4分别代表青光眼术后结膜纤维化疾病严重程度和预后的潜在新组织生物标志物。未来还需进行多个术后指标的纵向研究以验证这些潜在的纤维化生物标志物的作用。

Importance:Postsurgical fibrosis is a critical determinant of the long-term success of glaucoma surgery, but no reliable biomarkers are currently available to stratify the risk of scarring.Objective:To compare the clinical phenotype of patients with conjunctival fibrosis after glaucoma surgery with candidate gene expression tissue biomarkers of fibrosis.Design, Setting, and Participants:In this cross-sectional study, 42 patients were recruited at the time of glaucoma surgery at the Moorfields Eye Hospital from September 1, 2014, to September 1, 2016. The participants were divided into those with fibrosis and those without fibrosis.Main Outcomes and Measures:Genotype-phenotype correlations of the IL6 or PRG4 gene and detailed clinical phenotype. The IL6 and PRG4 protein expression in conjunctival tissues was also assessed using in situ immunohistochemical analysis. Central bleb area, maximal bleb area, and bleb height were graded on a scale of 1 to 5 (1 indicating 0%; 2, 25%; 3, 50%; 4, 75%; and 5, 100%). Bleb vascularity was graded on a scale of 1 to 5 (1 indicating avascularity; 2, normal; 3, mild; 4, moderate; and 5, severe hyperemia).Results:A total of 42 patients were recruited during the study period; 28 participants (67%) had previously undergone glaucoma surgery (fibrotic group) (mean [SD] age, 43.8 [3.6 years]; 16 [57%] female; 22 [79%] white), and 14 participants (33%) had not previously undergone glaucoma surgery (nonfibrotic group) (mean [SD] age, 47.7 [6.9] years; 4 [29%] female; 9 [64%] white). The fibrotic group had marked bleb scarring and vascularization and worse logMAR visual acuity. The mean (SD) grades were 1.4 (0.1) for central bleb area, 1.4 (0.1) for bleb height, and 3.4 (0.2) for bleb vascularity. The IL6 gene was upregulated in fibrotic cell lines (mean, 0.040) compared with nonfibrotic cell lines (mean, 0.011) (difference, 0.029; 95% CI, 0.015-0.043; P=.003). The PRG4 gene was also downregulated in fibrotic cell lines (0.002) compared with nonfibrotic cell lines (mean, 0.109; difference, 0.107; 95% CI, 0.104-0.110; P=.03). The study found a strong correlation between the IL6 gene and the number of glaucoma operations (r=0.94, P<.001) and logMAR visual acuity (r=0.64, P=.03). A moderate correlation was found between the PRG4 gene and the number of glaucoma operations (r=-0.72, P=.005) and logMAR visual acuity (r=-0.62, P=.03).Conclusions and Relevance:IL6 and PRG4 represent potential novel tissue biomarkers of disease severity and prognosis in conjunctival fibrosis after glaucoma surgery. Future longitudinal studies with multiple postoperative measures are needed to validate the effect of these potential biomarkers of fibrosis.


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