Comprehensive Proteomic Profiling of Exfoliation Glaucoma Via Mass Spectrometry Reveals SVEP1 as a Potential Biomarker.

IF 5 2区医学 Q1 OPHTHALMOLOGY

Investigative ophthalmology & visual science Pub Date : 2025-03-03 DOI:10.1167/iovs.66.3.19

Jiayong Li, Yuncheng Ma, Lingling Xie, Kaichen Zhuo, Yuxian He, Xin Ma, Shufen Zheng, Shicheng Guo, Yizhen Tang, Guzainuer Muhetaer, Mireayi Aizezi, Dan Zhang, Aizezi Wumaier, Xu Zhang, Chao Tang, Wei Wang, Wenyong Huang, Xinbo Gao

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引用次数: 0

Abstract

Purpose: This study investigated the proteomic landscape of exfoliation glaucoma to find potential biomarkers.

Methods: The study enrolled 34 patients diagnosed with either exfoliation syndrome with/without glaucoma or age-related cataract. Plasma proteins were analyzed through mass spectrometry and Mendelian randomization (MR) based on data from deCODE, FinnGen, Atherosclerosis Risk in Communities (ARIC), eQTLGen, and UK Biobank (UKB) cohorts to infer relationships.

Results: Among 2025 plasma proteins analyzed, 130 were differentially expressed in the exfoliation glaucoma group, which exhibited elevated intraocular pressure. Our proteomics data suggested that infection, immune responses including intestinal immune network, endocrine hormones, and complement and coagulation cascades are involved in the development of exfoliation glaucoma. Notably, there was a significant correlation between SVEP1 and exfoliation glaucoma (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.10 to 1.31, P = 0.0000428), with findings corroborated in an independent cohort. Further analysis predicted a protective role of LOXL1-AS1 in exfoliation glaucoma through its regulation of SVEP1 expression. In MR phenome-wide association studies, SVEP1 was associated with complications of exfoliation glaucoma. After multiple testing corrections, there was a tendency for SVEP1 to be associated with glaucoma (OR = 1.14, 95% CI = 1.11 to 1.16, P = 0.0000003) and type 2 diabetes (OR = 1.07, 95% CI = 1.05 to 1.08, P = 0.0000067).

Conclusions: Plasma proteomic analysis reveals that high expression of SVEP1 is a risk factor for exfoliation glaucoma, which potentially affects diabetes and is affected by estradiol or LOXL1-AS1. However, further research is needed to establish causality.

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脱落性青光眼的质谱综合蛋白质组学分析揭示SVEP1是一个潜在的生物标志物。

目的：研究脱落性青光眼的蛋白质组学特征，寻找潜在的生物标志物。方法：研究纳入了34例诊断为脱落综合征伴/不伴青光眼或老年性白内障的患者。基于deCODE、FinnGen、社区动脉粥样硬化风险（ARIC）、eQTLGen和UK Biobank （UKB）队列的数据，通过质谱和孟德尔随机化（MR）分析血浆蛋白，以推断两者之间的关系。结果：在分析的2025个血浆蛋白中，有130个蛋白在脱落性青光眼组中差异表达，表现为眼压升高。我们的蛋白质组学数据表明，感染、免疫反应包括肠道免疫网络、内分泌激素、补体和凝血级联反应参与了脱落性青光眼的发展。值得注意的是，SVEP1与脱落性青光眼之间存在显著相关性（优势比[OR] = 1.20, 95%可信区间[CI] = 1.10 ~ 1.31, P = 0.0000428），这一发现在一个独立队列中得到了证实。进一步分析预测LOXL1-AS1通过调控SVEP1的表达对脱落性青光眼具有保护作用。在MR全表型关联研究中，SVEP1与剥脱性青光眼的并发症相关。经过多次检验校正，SVEP1倾向于与青光眼（OR = 1.14, 95% CI = 1.11 ~ 1.16, P = 0.0000003）和2型糖尿病（OR = 1.07, 95% CI = 1.05 ~ 1.08, P = 0.0000067）相关。结论：血浆蛋白质组学分析显示SVEP1高表达是脱落性青光眼的危险因素，可能影响糖尿病，并受雌二醇或LOXL1-AS1的影响。然而，需要进一步的研究来确定因果关系。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Investigative ophthalmology & visual science 医学-眼科学

CiteScore

6.90

自引率

4.50%

发文量

339

审稿时长

1 months

期刊介绍： Investigative Ophthalmology & Visual Science (IOVS), published as ready online, is a peer-reviewed academic journal of the Association for Research in Vision and Ophthalmology (ARVO). IOVS features original research, mostly pertaining to clinical and laboratory ophthalmology and vision research in general.