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青光眼手术早期失败中结膜滤过泡纤维组织增生的基因和蛋白质差异表达

Differential Gene and Protein Expression of Conjunctival Bleb Hyperfibrosis in Early Failure of Glaucoma Surgery.

作者信息

Millá Elena, Ventura-Abreu Néstor, Vendrell Cristina, Muniesa Maria Jesús, Pazos Marta, Gasull Xavier, Comes Núria

机构信息

Hospital Clínic de Barcelona, Institut Clinic d'Oftalmologia, ICOF, Sabino Arana nº1, 08028 Barcelona, Spain.

Institut Comtal d'Oftalmologia, Innova Ocular-ICO Barcelona, Via Augusta 48, 08006 Barcelona, Spain.

出版信息

Int J Mol Sci. 2023 Jul 26;24(15):11949. doi: 10.3390/ijms241511949.

Abstract

The early failure of glaucoma surgery is mainly caused by over-fibrosis at the subconjunctival space, causing obliteration of the filtration bleb. Because fibrosis has a suspected basis of genetic predisposition, we have undertaken a prospective study to identify upregulated profibrotic genes in a population of glaucoma patients with signs of conjunctival fibrosis and early postoperative surgical failure. Clinical data of re-operated fibrosis patients, hyperfibrosis patients who re-operated more than once in a short time, and control patients with no fibrosis were recorded and analyzed at each follow-up visit. Conjunctival-Tenon surgical specimens were obtained intraoperatively to evaluate the local expression of a panel of genes potentially associated with fibrosis. In order to correlate gene expression signatures with protein levels, we quantified secreted proteins in primary cultures of fibroblasts from patients. Expression of , , , and was induced in the conjunctiva of hyperfibrosis patients. VEGFA and IL8 protein levels were also increased in fibroblast supernatants. We propose that an increase in these proteins could be useful in detecting conjunctival fibrosis in glaucoma patients undergoing filtering surgery. Molecular markers could be crucial for early detection of patients at high risk of failure of filtration surgery, leading to more optimal and personalized treatments.

摘要

青光眼手术早期失败主要是由结膜下间隙过度纤维化导致滤过泡闭塞引起的。由于纤维化存在遗传易感性的潜在基础,我们开展了一项前瞻性研究,以确定在有结膜纤维化体征和术后早期手术失败的青光眼患者群体中上调的促纤维化基因。在每次随访时记录并分析再次手术的纤维化患者、短期内多次再次手术的高纤维化患者以及无纤维化的对照患者的临床数据。术中获取结膜-提上睑肌手术标本,以评估一组可能与纤维化相关基因的局部表达。为了将基因表达特征与蛋白质水平相关联,我们对患者成纤维细胞原代培养物中的分泌蛋白进行了定量。高纤维化患者结膜中 、 、 和 的表达上调。成纤维细胞上清液中的血管内皮生长因子A(VEGFA)和白细胞介素8(IL8)蛋白水平也升高。我们认为这些蛋白质水平的升高可能有助于检测接受滤过手术的青光眼患者的结膜纤维化。分子标志物对于早期检测滤过手术失败高风险患者可能至关重要,从而实现更优化和个性化的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b76a/10418990/4a52b528b923/ijms-24-11949-g001.jpg

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