{"title":"Identification of novel drug targets for primary open angle glaucoma and its potential side-effects by human plasma proteome.","authors":"Da-Dong Jia, Qing-Ao Xiao, Shi-Yi Song, Meng Pan, Hao Hu, Kai-Li Wu, Jia-Bing Ran, Liang Liang","doi":"10.18240/ijo.2025.08.07","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>To explore whether plasma proteins serve as potential therapeutic targets for primary open angle glaucoma (POAG) based on a Mendelian randomization (MR) study.</p><p><strong>Methods: </strong>Large-scale protein quantitative trait loci (pQTLs) data from the Icelandic deCODE database and two large POAG Genome-Wide Association Study (GWAS) summary datasets were used in this study. Causal associations between plasma proteins and POAG were identified using summary-data-based MR (SMR) analysis and the heterogeneity in dependent instruments (HEIDI) test. Colocalization analysis was then conducted to assess the genetic associations between these two factors. Phenotype-wide MR analysis was performed to validate protein targets as potential drug targets and to evaluate potential side effects. Finally, protein-protein interactions (PPI) were studied, and the Drug-Gene Interaction Database (DGIDb) was used to identify associations between drugs and the identified proteins.</p><p><strong>Results: </strong>Four proteins (SVEP1, TMEM190, ROBO1, and ENPP5) were identified as potential drug targets in this study. Phenome-wide MR analysis showed that SVEP1, ROBO1, and ENPP5 were not associated with adverse effects, while TMEM190 was linked to nerve root and plexus disorders, as well as subarachnoid hemorrhage. Ticagrelor was suggested as a potential new drug for the treatment of glaucoma by regulating SVEP1.</p><p><strong>Conclusion: </strong>Four plasma proteins-SVEP1, TMEM190, ROBO1, and ENPP5-are identified as potential therapeutic targets for POAG through an MR approach. Phenome-wide MR analysis reveals that SVEP1, ROBO1, and ENPP5 are not associated with adverse effects, while TMEM190 is linked to nerve root and plexus disorders, as well as subarachnoid hemorrhage. Ticagrelor is proposed as a potential therapeutic drug for glaucoma by regulating SVEP1. These findings highlight the potential of plasma proteins as drug targets for POAG and provide valuable insights for further research.</p>","PeriodicalId":14312,"journal":{"name":"International journal of ophthalmology","volume":"18 8","pages":"1470-1477"},"PeriodicalIF":1.8000,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311459/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International journal of ophthalmology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.18240/ijo.2025.08.07","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"OPHTHALMOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Aim: To explore whether plasma proteins serve as potential therapeutic targets for primary open angle glaucoma (POAG) based on a Mendelian randomization (MR) study.
Methods: Large-scale protein quantitative trait loci (pQTLs) data from the Icelandic deCODE database and two large POAG Genome-Wide Association Study (GWAS) summary datasets were used in this study. Causal associations between plasma proteins and POAG were identified using summary-data-based MR (SMR) analysis and the heterogeneity in dependent instruments (HEIDI) test. Colocalization analysis was then conducted to assess the genetic associations between these two factors. Phenotype-wide MR analysis was performed to validate protein targets as potential drug targets and to evaluate potential side effects. Finally, protein-protein interactions (PPI) were studied, and the Drug-Gene Interaction Database (DGIDb) was used to identify associations between drugs and the identified proteins.
Results: Four proteins (SVEP1, TMEM190, ROBO1, and ENPP5) were identified as potential drug targets in this study. Phenome-wide MR analysis showed that SVEP1, ROBO1, and ENPP5 were not associated with adverse effects, while TMEM190 was linked to nerve root and plexus disorders, as well as subarachnoid hemorrhage. Ticagrelor was suggested as a potential new drug for the treatment of glaucoma by regulating SVEP1.
Conclusion: Four plasma proteins-SVEP1, TMEM190, ROBO1, and ENPP5-are identified as potential therapeutic targets for POAG through an MR approach. Phenome-wide MR analysis reveals that SVEP1, ROBO1, and ENPP5 are not associated with adverse effects, while TMEM190 is linked to nerve root and plexus disorders, as well as subarachnoid hemorrhage. Ticagrelor is proposed as a potential therapeutic drug for glaucoma by regulating SVEP1. These findings highlight the potential of plasma proteins as drug targets for POAG and provide valuable insights for further research.
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
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International Council of Ophthalmology(ICO), PubMed, PMC, American Academy of Ophthalmology, Asia-Pacific, Thomson Reuters, The Charlesworth Group, Crossref,Scopus,Publons, DOAJ etc.
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