Causal role of oxidative stress in age-related macular degeneration: a bidirectional Mendelian randomization study.

IF 1.8 4区医学 Q2 OPHTHALMOLOGY

International journal of ophthalmology Pub Date : 2025-07-18 eCollection Date: 2025-01-01 DOI:10.18240/ijo.2025.07.14

Li-Yun Yuan, Wang-Ming Su, Liang-Pin Li, Xiao-Feng Tian, Xue-Li Zheng, Xiao-Yong Yuan

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引用次数: 0

Abstract

Aim: To elucidate causal pathways between oxidative biomarkers and age-related macular degeneration (AMD) phenotypes.

Methods: A bidirectional Mendelian randomization (MR) analytical protocol was implemented, which utilized genome-wide association study (GWAS) summary statistics derived from the IEU OpenGWAS repositories. The investigation focused on 11 oxidative stress markers and AMD phenotypes, encompassing both wet and dry subtypes. The MR methodology incorporated inverse-variance weighted (IVW) calculations, MR-Egger statistical regression, weighted median approximation, and weighted mode assessments to estimate causative relationships. Sensitivity evaluations were conducted to verify result robustness and identify potential pleiotropy.

Results: Genetically predicted elevated catalase (CAT) concentrations demonstrated significant associations with heightened risks of overall AMD (IVW OR=1.084, 95%CI: 1.021-1.151, P=0.008) and wet AMD phenotype (IVW OR=1.113, 95%CI: 1.047-1.247, P=0.007). Higher genetically predicted albumin concentrations corresponded with reduced AMD risk (IVW OR=0.827, 95%CI: 0.715-0.957, P=0.013) but increased wet AMD risk (IVW OR=1.229, 95%CI: 1.036-1.458, P=0.018). Reverse MR analysis revealed that genetically predicted dry AMD exhibited significant association with reduced albumin levels (IVW OR=0.987, 95%CI: 0.979-0.996, P=0.004), while wet AMD corresponded with decreased total bilirubin (TBIL) and paraoxonase (PON) activity.

Conclusion: The results offer strong support for a causal link between markers of oxidative stress and the development of AMD, indicating that oxidative processes play a role in driving the disease progression.

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氧化应激在年龄相关性黄斑变性中的因果作用：一项双向孟德尔随机研究。

目的：阐明氧化生物标志物与年龄相关性黄斑变性（AMD）表型之间的因果关系。方法：采用双向孟德尔随机化（MR）分析方案，利用来自IEU OpenGWAS数据库的全基因组关联研究（GWAS）汇总统计数据。研究重点是11种氧化应激标记物和AMD表型，包括湿型和干型。MR方法结合了反方差加权（IVW）计算、MR- egger统计回归、加权中位数近似和加权模式评估来估计因果关系。进行敏感性评估以验证结果的稳健性并识别潜在的多效性。结果：基因预测的过氧化氢酶（CAT）浓度升高与整体AMD （IVW OR=1.084, 95%CI: 1.021-1.151， P=0.008）和湿性AMD表型（IVW OR=1.113, 95%CI: 1.047-1.247， P=0.007）的风险增加显著相关。较高的遗传预测白蛋白浓度与AMD风险降低相关（IVW OR=0.827, 95%CI: 0.715-0.957， P=0.013），但与湿性AMD风险增加相关（IVW OR=1.229, 95%CI: 1.036-1.458， P=0.018）。反向磁共振分析显示，遗传预测的干性AMD与白蛋白水平降低显著相关（IVW OR=0.987, 95%CI: 0.979-0.996， P=0.004），而湿性AMD与总胆红素（TBIL）和对氧磷酶（PON）活性降低相关。结论：该结果有力地支持氧化应激标志物与AMD发展之间的因果关系，表明氧化过程在推动疾病进展中发挥作用。

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

International journal of ophthalmology Medicine-Ophthalmology

CiteScore

2.50

自引率

7.10%

发文量

3141

审稿时长

4-8 weeks

期刊介绍： · International Journal of Ophthalmology-IJO (English edition) is a global ophthalmological scientific publication and a peer-reviewed open access periodical (ISSN 2222-3959 print, ISSN 2227-4898 online). This journal is sponsored by Chinese Medical Association Xi’an Branch and obtains guidance and support from WHO and ICO (International Council of Ophthalmology). It has been indexed in SCIE, PubMed, PubMed-Central, Chemical Abstracts, Scopus, EMBASE , and DOAJ. IJO JCR IF in 2017 is 1.166. IJO was established in 2008, with editorial office in Xi’an, China. It is a monthly publication. General Scientific Advisors include Prof. Hugh Taylor (President of ICO); Prof.Bruce Spivey (Immediate Past President of ICO); Prof.Mark Tso (Ex-Vice President of ICO) and Prof.Daiming Fan (Academician and Vice President, Chinese Academy of Engineering. International Scientific Advisors include Prof. Serge Resnikoff (WHO Senior Speciatist for Prevention of blindness), Prof. Chi-Chao Chan (National Eye Institute, USA) and Prof. Richard L Abbott (Ex-President of AAO/PAAO) et al. Honorary Editors-in-Chief: Prof. Li-Xin Xie(Academician of Chinese Academy of Engineering/Honorary President of Chinese Ophthalmological Society); Prof. Dennis Lam (President of APAO) and Prof. Xiao-Xin Li (Ex-President of Chinese Ophthalmological Society). Chief Editor: Prof. Xiu-Wen Hu (President of IJO Press). Editors-in-Chief: Prof. Yan-Nian Hui (Ex-Director, Eye Institute of Chinese PLA) and Prof. George Chiou (Founding chief editor of Journal of Ocular Pharmacology & Therapeutics). Associate Editors-in-Chief include: Prof. Ning-Li Wang (President Elect of APAO); Prof. Ke Yao (President of Chinese Ophthalmological Society) ; Prof.William Smiddy (Bascom Palmer Eye instituteUSA) ; Prof.Joel Schuman (President of Association of University Professors of Ophthalmology,USA); Prof.Yizhi Liu (Vice President of Chinese Ophtlalmology Society); Prof.Yu-Sheng Wang (Director of Eye Institute of Chinese PLA); Prof.Ling-Yun Cheng (Director of Ocular Pharmacology, Shiley Eye Center, USA). IJO accepts contributions in English from all over the world. It includes mainly original articles and review articles, both basic and clinical papers. Instruction is Welcome Contribution is Welcome Citation is Welcome Cooperation organization International Council of Ophthalmology(ICO), PubMed, PMC, American Academy of Ophthalmology, Asia-Pacific, Thomson Reuters, The Charlesworth Group, Crossref,Scopus,Publons, DOAJ etc.