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Identification and validation of key biomarkers and potential therapeutic targets for primary open-angle glaucoma

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Abstract

Primary open-angle glaucoma (POAG) is a prevalent cause of blindness worldwide, resulting in degeneration of retinal ganglion cells and permanent damage to the optic nerve. However, the underlying pathogenetic mechanisms of POAG are currently indistinct, and there has been no effective nonsurgical treatment regimen. The objective of this study is to identify novel biomarkers and potential therapeutic targets for POAG. The mRNA expression microarray datasets GSE27276 and GSE138125, as well as the single-cell high-throughput RNA sequencing (scRNA-seq) dataset GSE148371 were utilized to screen POAG-related differentially expressed genes (DEGs). Functional enrichment analyses, protein-protein interaction (PPI) analysis, and weighted gene co-expression network analysis (WGCNA) of the DEGs were performed. Subsequently, the hub genes were validated at a single-cell level, where trabecular cells were annotated, and the mRNA expression levels of target genes in different cell clusters were analyzed. Immunofluorescence and quantitative real-time PCR (qPCR) were performed for further validation. DEGs analysis identified 43 downregulated and 32 upregulated genes in POAG, which were mainly enriched in immune-related pathways, oxidative stress, and endoplasmic reticulum (ER) stress. PPI networks showed that FN1 and DUSP1 were the central hub nodes, while GPX3 and VAV3 were screened out as hub genes through WGCNA and subsequently validated by qPCR. Finally, FN1, GPX3, and VAV3 were determined to be pivotal core genes via single-cell validation. The relevant biomarkers involved in the pathogenesis of POAG, may serve as potential therapeutic targets. Further studies are necessary to unveil the mechanisms underlying the expression variations of these genes in POAG.

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Acknowledgements

This work was supported by Beijing Traditional Chinese Medicine Technology Development Fund Project (JJ2018-50), the National Natural Science Foundation of China (81901202), Beijing Natural Science Foundation (7222217), the Capital Health Research and Development of Special (2022-4-40918), and Clinical Medicine Plus X-Young Scholars Project, Peking University, the Fundamental Research Funds for the Central Universities (PKU2021LCXQ007). Thanks to all the participants for their valuable contributions.

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  1. Contributed equally to this work

Authors and Affiliations

  1. Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, 100730, China

    Jian Wu, Lijie Pan, Hongyi Liu, Sirui Zhu, Shuwen Wei & Ningli Wang

  2. Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China

    Caixia Lin

  3. Department of Neurosurgery, Peking University Third Hospital, Center for Precision Neurosurgery and Oncology of Peking University Health Science Center, Beijing, 100191, China

    Chenlong Yang, Xiaofang Zhao & Weihai Liu

  4. North America Medical Education Foundation, Union City, CA, 94539, USA

    Chenlong Yang

  5. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China

    Xu Jia, Qi Zhang & Yehong Zhuo

  6. Spencer Center for Vision Research, Byers Eye Institute, School of Medicine, Stanford University, Palo Alto, CA, 94304, USA

    Ziyu Yu

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  1. Jian Wu
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  2. Caixia Lin
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  3. Chenlong Yang
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Correspondence to Yehong Zhuo or Ningli Wang.

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Wu, J., Lin, C., Yang, C. et al. Identification and validation of key biomarkers and potential therapeutic targets for primary open-angle glaucoma. Sci. China Life Sci. 66, 2837–2850 (2023). https://doi.org/10.1007/s11427-022-2344-5

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  • DOI: https://doi.org/10.1007/s11427-022-2344-5

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