Identification of Biomarkers for Oxidative Stress in Age-Related Macular Degeneration: Combining Transcriptomics and Mendelian Randomization Analysis.

IF 2.6 3区医学 Q2 OPHTHALMOLOGY

Translational Vision Science & Technology Pub Date : 2025-08-01 DOI:10.1167/tvst.14.8.42

Wei Chen, Zijing Li, Xiaoyan Zhou, Chunli Li, Yuting Lin

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引用次数: 0

Abstract

Purpose: Oxidative stress has long been recognized as a significant influence in the pathophysiology of age-related macular degeneration (AMD). Therefore there is a need to explore the relationship between oxidative stress-related biomarkers and AMD.

Methods: Based on Gene Expression Omnibus database-Gene Expression Omnibus Series (GSE)29801 and GSE135092 datasets, three machine learning methods were used to screen biomarkers. The Wilcoxon test was used to compare the percentage of immune cells in control and AMD samples. The causal relationship between biomarkers and AMD was explored in a series of Mendelian randomization (MR) analyses. Ultimately, the expression levels of biomarkers were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in the simulated AMD cell model.

Results: A total of 16 differentially expressed oxidative stress-related genes (DE-OSRGs) were screened. Functional enrichment analysis indicated that DE-OSRGs participated in cellular senescence, cell cycle regulation, and PPAR signaling pathways. Machine learning methods were used to screen for five biomarkers (GFAP, Stearoyl-CoA desaturase [SCD], BCKDHB, GPX8, and MSRB2). The qRT-PCR results showed that the expression levels of five biomarkers were significantly different between the simulated AMD cell model and control groups. Spearman correlation analysis showed that GPX8 had the highest positive correlation with M2 macrophages (correlation coefficient [cor] = 0.36, P < 0.01), and SCD had a strong negative correlation with eosinophils (cor = -0.28, P < 0.05). MR results revealed that BCKDHB played a crucial role as a risk factor for AMD (odds ratio > 1, P < 0.05).

Conclusions: This study screened the biomarkers related to oxidative stress in AMD, providing a certain theoretical basis for the prevention and clinical diagnosis of AMD.

Translational relevance: Identifying biomarkers with diagnostic value for AMD could provide new understanding of its pathogenesis, and open up potential targets for clinical intervention.

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年龄相关性黄斑变性氧化应激生物标志物的鉴定：结合转录组学和孟德尔随机化分析。

目的：氧化应激在老年性黄斑变性（AMD）的病理生理中一直被认为具有重要影响。因此，有必要探索氧化应激相关生物标志物与AMD之间的关系。方法：基于基因表达Omnibus数据库-基因表达Omnibus系列（GSE）29801和GSE135092数据集，采用三种机器学习方法筛选生物标志物。使用Wilcoxon试验比较对照和AMD样品中免疫细胞的百分比。通过一系列孟德尔随机化（MR）分析，探讨了生物标志物与AMD之间的因果关系。最终，在模拟AMD细胞模型中，通过定量实时聚合酶链反应（qRT-PCR）验证生物标志物的表达水平。结果：共筛选到16个氧化应激相关差异表达基因（DE-OSRGs）。功能富集分析表明，DE-OSRGs参与细胞衰老、细胞周期调控和PPAR信号通路。使用机器学习方法筛选五种生物标志物（GFAP，硬脂酰辅酶a去饱和酶[SCD]， BCKDHB， GPX8和MSRB2）。qRT-PCR结果显示，模拟AMD细胞模型与对照组间5种生物标志物的表达水平有显著差异。Spearman相关分析显示GPX8与M2巨噬细胞呈正相关最高（相关系数[cor] = 0.36, P < 0.01）， SCD与嗜酸性粒细胞呈强负相关（cor = -0.28, P < 0.05）。MR结果显示BCKDHB是AMD的重要危险因素（优势比bbb1， P < 0.05）。结论：本研究筛选了AMD中与氧化应激相关的生物标志物，为AMD的预防和临床诊断提供了一定的理论依据。转化相关性：识别具有诊断价值的生物标志物可以为AMD的发病机制提供新的认识，并为临床干预开辟潜在靶点。

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

Translational Vision Science & Technology Engineering-Biomedical Engineering

CiteScore

5.70

自引率

3.30%

发文量

346

审稿时长

25 weeks

期刊介绍： Translational Vision Science & Technology (TVST), an official journal of the Association for Research in Vision and Ophthalmology (ARVO), an international organization whose purpose is to advance research worldwide into understanding the visual system and preventing, treating and curing its disorders, is an online, open access, peer-reviewed journal emphasizing multidisciplinary research that bridges the gap between basic research and clinical care. A highly qualified and diverse group of Associate Editors and Editorial Board Members is led by Editor-in-Chief Marco Zarbin, MD, PhD, FARVO. The journal covers a broad spectrum of work, including but not limited to: Applications of stem cell technology for regenerative medicine, Development of new animal models of human diseases, Tissue bioengineering, Chemical engineering to improve virus-based gene delivery, Nanotechnology for drug delivery, Design and synthesis of artificial extracellular matrices, Development of a true microsurgical operating environment, Refining data analysis algorithms to improve in vivo imaging technology, Results of Phase 1 clinical trials, Reverse translational ("bedside to bench") research. TVST seeks manuscripts from scientists and clinicians with diverse backgrounds ranging from basic chemistry to ophthalmic surgery that will advance or change the way we understand and/or treat vision-threatening diseases. TVST encourages the use of color, multimedia, hyperlinks, program code and other digital enhancements.