病理性近视的多组学研究现状及其进展

doi:10.12677/acm.2026.1682766

期刊菜单

病理性近视的多组学研究现状及其进展
Multi-Omics Research in Pathological Myopia: Current Status and Progress

DOI: 10.12677/acm.2026.1682766, PDF,
作者: 周卓雅, 陈璐：暨南大学第二临床医学院，深圳市眼科医院，广东深圳
关键词: 病理性近视；多组学；基因组学；表观遗传学；生物标志物；Pathologic Myopia； Multi-Omics； Genomics； Epigenetics； Biomarkers

摘要: 病理性近视(pathologic myopia, PM)是以眼轴过度延长和后极部特征性病理改变为特征的致盲性眼病，其发病机制涉及遗传、环境及表观遗传等多层次因素的复杂交互。近年来，多组学技术的迅猛发展使PM研究从单一分子层面迈向系统整合。基因组学通过GWAS和全外显子/全基因组测序鉴定了LILRB2、KDELR3等新易感基因，并揭示了PM与遗传性视网膜疾病的遗传重叠；表观遗传学研究强调DNA甲基化、组蛋白修饰(如H3K27me3)及非编码RNA在环境–遗传对话中的桥梁作用；转录组学(含单细胞测序)和蛋白质组学共同阐明了巩膜ECM重塑、TGF-β信号、炎症及氧化应激等核心通路；代谢组学与微生物组学则发现房水、血浆及肠道菌群来源的代谢物(如3-IAA)参与眼轴调控，并提出“肠–眼轴”新视角。多组学整合策略不仅深化了对PM分子机制的理解，还筛选出ANGPTL7、BDH1等潜在生物标志物及治疗靶点。未来，跨尺度、多维度的组学融合将推动PM的早期预警、分子分型及精准干预。

Abstract: Pathologic myopia (PM) is a sight-threatening ocular disease characterized by excessive axial elongation and characteristic posterior segment pathological changes. Its pathogenesis involves complex interactions among genetic, environmental, and epigenetic factors across multiple biological layers. In recent years, the rapid advancement of multi-omics technologies has propelled PM research from a single-molecule level toward systemic integration. Genomics, through genome-wide association studies (GWAS) and whole-exome/whole-genome sequencing, has identified novel susceptibility genes such as LILRB2 and KDELR3, and has revealed genetic overlaps between PM and inherited retinal dystrophies. Epigenetics has underscored the bridging role of DNA methylation, histone modifications (e.g., H3K27me3), and non-coding RNAs in environment–genome crosstalk. Transcriptomics, including single-cell sequencing, together with proteomics, has collectively elucidated core pathways involved in scleral extracellular matrix (ECM) remodeling, TGF-β signaling, inflammation, and oxidative stress. Metabolomics and microbiome analyses have identified metabolites derived from aqueous humor, plasma, and gut microbiota (e.g., 3-indoleacetic acid, 3-IAA) that participate in axial length regulation, thereby introducing the novel “gut–eye axis” perspective. Integrative multi-omics strategies have not only deepened our mechanistic understanding of PM but also enabled the screening of potential biomarkers and therapeutic targets, including ANGPTL7 and BDH1. Looking forward, cross-scale, multi-dimensional omics integration will facilitate early warning, molecular subtyping, and precision intervention for PM.

文章引用：周卓雅, 陈璐. 病理性近视的多组学研究现状及其进展[J]. 临床医学进展, 2026, 16(8): 16-25. https://doi.org/10.12677/acm.2026.1682766

参考文献

[1]	Ohno-Matsui, K., Kawasaki, R., Jonas, J.B., Cheung, C.M.G., Saw, S., Verhoeven, V.J.M., et al. (2015) International Photographic Classification and Grading System for Myopic Maculopathy. American Journal of Ophthalmology, 159, 877-883.e7. https://doi.org/10.1016/j.ajo.2015.01.022
[2]	Holden, B.A., Fricke, T.R., Wilson, D.A., Jong, M., Naidoo, K.S., Sankaridurg, P., et al. (2016) Global Prevalence of Myopia and High Myopia and Temporal Trends from 2000 through 2050. Ophthalmology, 123, 1036-1042. https://doi.org/10.1016/j.ophtha.2016.01.006
[3]	Yii, F., Nguyen, L., Strang, N., Bernabeu, M.O., Tatham, A.J., MacGillivray, T., et al. (2024) Factors Associated with Pathologic Myopia Onset and Progression: A Systematic Review and Meta-Analysis. Ophthalmic and Physiological Optics, 44, 963-976. https://doi.org/10.1111/opo.13312
[4]	Voogelaar, M., Tedja, M.S., Guggenheim, J.A., Saw, S., Tjon-Fo-Sang, M., Mackey, D.A., et al. (2025) IMI-Myopia Genetics Report. Investigative Ophthalmology & Visual Science, 66, 22. https://doi.org/10.1167/iovs.66.13.22
[5]	Dong, X.X., Chen, D.L., Chen, H.M., et al. (2024) DNA Methylation Biomarkers and Myopia: A Multi-Omics Study Integrating GWAS, mQTL and eQTL Data. Clinical Epigenetics, 16, Article No. 157. https://doi.org/10.1186/s13148-024-01772-1
[6]	Shi, X.H., Dong, L., Zhang, R.H., Zhou, W.D., Li, Y.F., Wu, H.T., et al. (2023) Reduction of Experimental Ocular Axial Elongation by Neuregulin-1 Antibody. Frontiers in Medicine, 10, Article 1277180. https://doi.org/10.3389/fmed.2023.1277180
[7]	Yao, Y., Wei, L., Chen, Z., Li, H., Qi, J., Wu, Q., et al. (2023) Single-Cell RNA Sequencing: Inhibited NotcH2 Signalling Underlying the Increased Lens Fibre Cells Differentiation in High Myopia. Cell Proliferation, 56, e13412. https://doi.org/10.1111/cpr.13412
[8]	He, J., Ye, L., Xu, H., Yang, H., Shen, J., Li, M., et al. (2024) Multi-Omics Analysis Reveals a Novel NFE2L3 Variant Impairing Choroidal Vasculature Development in High Myopia and Myopic Maculopathy. National Science Review, 12, nwae291. https://doi.org/10.1093/nsr/nwae291
[9]	Jiang, L., Huang, L., Dai, C., Zheng, R., Miyake, M., Mori, Y., et al. (2024) Genome‐Wide Association Analysis Identifies LILRB2 Gene for Pathological Myopia. Advanced Science, 11, e2308968. https://doi.org/10.1002/advs.202308968
[10]	Guggenheim, J.A., Clark, R., Cui, J., Terry, L., Patasova, K., Haarman, A.E.G., et al. (2022) Whole Exome Sequence Analysis in 51624 Participants Identifies Novel Genes and Variants Associated with Refractive Error and Myopia. Human Molecular Genetics, 31, 1909-1919. https://doi.org/10.1093/hmg/ddac004
[11]	Yuan, J., Zhuang, Y., Liu, X., Zhang, Y., Li, K., Chen, Z.J., et al. (2024) Exome-Wide Association Study Identifies KDELR3 Mutations in Extreme Myopia. Nature Communications, 15, Article No. 6703. https://doi.org/10.1038/s41467-024-50580-x
[12]	Han, C., Wu, S., Yang, Y., Yang, X. and Li, H. (2026) Whole-Exome Sequencing for the Genetic Diagnosis of Early-Onset High Myopia and Associated Hereditary Eye Disorders. BMC Medical Genomics, 19, Article No. 51. https://doi.org/10.1186/s12920-026-02334-5
[13]	Šenk, U., Čižman, B., Writzl, K. and Tekavčič Pompe, M. (2024) Genetic Background of High Myopia in Children. PLOS ONE, 19, e0313121. https://doi.org/10.1371/journal.pone.0313121
[14]	Zhang, Y., Yang, Z., Zhang, M., Yang, Y., Ma, Z., Wu, M., et al. (2025) Research Progress of Epigenetic Modifications in Myopia. International Journal of Medical Sciences, 22, 3084-3100. https://doi.org/10.7150/ijms.110640
[15]	Lei, Y., Lin, X., Ling, X., Tan, Y., Yuan, J., Li, Y., et al. (2026) Intermittent Myopic Visual Exposure Triggers Myopia Progression via H3K27me3. Genome Medicine, 18, Article No. 77. https://doi.org/10.1186/s13073-026-01652-8
[16]	Xu, J., Wang, L. and Shen, Z. (2026) Associations between Mechanical Stress and Epigenetic Modifications in Outer Retinal Layer Remodeling in High Myopia. Frontiers in Medicine, 13, Article 1780606. https://doi.org/10.3389/fmed.2026.1780606
[17]	Hu, Y., Fan, Y., Li, N., Xu, C. and Wang, J. (2024) Expression of LncRNAs in Anterior Capsule of Lens in Patients with Pathologic Myopia Complicated with Cataract. International Ophthalmology, 45, Article No. 10. https://doi.org/10.1007/s10792-024-03366-5
[18]	Guan, M., Zhang, B., Wu, W., Li, Y. and Zhang, F. (2025) The Role of circFAM53B in Regulating Choroidal Vascular Function in Pathological Myopia. Current Eye Research, 50, 758-770. https://doi.org/10.1080/02713683.2025.2477550
[19]	Wang, X., Lin, Q., Liu, S., Li, X., Kong, X., Wang, Y., et al. (2023) LncRNA-XR_002792574.1-Mediated ceRNA Network Reveals Potential Biomarkers in Myopia-Induced Retinal Ganglion Cell Damage. Journal of Translational Medicine, 21, Article No. 785. https://doi.org/10.1186/s12967-023-04662-x
[20]	Palumaa, T., Balamurugan, S. and Pardue, M.T. (2025) Meta-Analysis of Retinal Transcriptome Profiling Studies in Animal Models of Myopia. Frontiers in Medicine, 11, Article 1479891. https://doi.org/10.3389/fmed.2024.1479891
[21]	Chen, T., Liu, S., Yang, Z., Feng, S., Fang, W., Lu, X., et al. (2024) Investigation Roles of Adamts1 and Adamts5 in Scleral Fibroblasts under Hypoxia and Mice with Form-Deprived Myopia. Experimental Eye Research, 247, Article 110026. https://doi.org/10.1016/j.exer.2024.110026
[22]	Stone, R.A., Tobias, J.W., Wei, W., Schug, J., Wang, X., Zhang, L., et al. (2024) Diurnal Retinal and Choroidal Gene Expression Patterns Support a Role for Circadian Biology in Myopia Pathogenesis. Scientific Reports, 14, Article No. 533. https://doi.org/10.1038/s41598-023-50684-2
[23]	Cheng, Y., Gu, S., Lu, X. and Pei, C. (2025) The Advance of Single-Cell RNA Sequencing Applications in Ocular Physiology and Disease Research. Biomolecules, 15, Article 1120. https://doi.org/10.3390/biom15081120
[24]	Yao, Y., Chen, Z., Wu, Q., Lu, Y., Zhou, X. and Zhu, X. (2023) Single-Cell RNA Sequencing of Retina Revealed Novel Transcriptional Landscape in High Myopia and Underlying Cell-Type-Specific Mechanisms. MedComm, 4, e372. https://doi.org/10.1002/mco2.372
[25]	Zhu, H., Chen, W., Ling, X., Jiao, S., Yu, L., Liu, H., et al. (2025) Decreased Scleral Wnt5ahi Fibroblasts Exacerbate Myopia Progression by Disrupting Extracellular Matrix Homeostasis in Mice. Nature Communications, 17, Article No. 554. https://doi.org/10.1038/s41467-025-67246-x
[26]	Ku, H., Chen, J.J., Chen, W., Tien, P., Lin, H., Wan, L., et al. (2024) The Role of Transforming Growth Factor Beta in Myopia Development. Molecular Immunology, 167, 34-42. https://doi.org/10.1016/j.molimm.2024.01.011
[27]	Wen, Y., Ren, C., Zhu, L., Huang, L., Qi, H., Yu, W., et al. (2024) Unmasking of Molecular Players: Proteomic Profiling of Vitreous Humor in Pathologic Myopia. BMC Ophthalmology, 24, Article No. 352. https://doi.org/10.1186/s12886-024-03584-6
[28]	Su, W., Qiu, P., Li, Y., Xie, P. and Yuan, X. (2025) Integrated Genomics Reveals Cellular Senescence-Driven Molecular Networks and Immune Crosstalk in Myopia Pathogenesis. Journal of Cell Communication and Signaling, 19, e70045. https://doi.org/10.1002/ccs3.70045
[29]	Song, Y., Xu, Z., Li, H., Xie, Y., Zhao, L., Feng, J., et al. (2025) Proteomic and Phosphoproteomic Characteristics of the Retina, Choroid, and Sclera in Guinea Pigs with Form-Deprivation Myopia. Molecular & Cellular Proteomics, 24, Article 101069. https://doi.org/10.1016/j.mcpro.2025.101069
[30]	Li, H., Shi, X., Dong, L., Yu, C., Li, Y., Zhang, R., et al. (2025) Transcriptomic and Proteomic Analyses of Sclera in Lens-Induced Myopic Guinea Pigs. BMC Genomics, 26, Article No. 242. https://doi.org/10.1186/s12864-025-11422-2
[31]	Liu, Y., Chen, X., Kou, J., Wen, X. and Liu, L. (2026) Integrated Proteomic and Nitrosylomic Profiling Suggests a Role for S-Nitrosylation in Choroidal Dysregulation during Myopia Pathogenesis. Experimental Eye Research, 266, Article 110909. https://doi.org/10.1016/j.exer.2026.110909
[32]	Hui, J., Cui, X. and Han, Q. (2026) Multi-Omics Integration Uncovers Key Molecular Mechanisms and Therapeutic Targets in Myopia and Pathological Myopia. Asia-Pacific Journal of Ophthalmology, 15, Article 100277. https://doi.org/10.1016/j.apjo.2026.100277
[33]	Jiang, L., Koh, J.H.Z., Seah, S.H.Y., Dan, Y.S., Wang, Z., Chan, X., et al. (2024) Key Role for Inflammation-Related Signaling in the Pathogenesis of Myopia Based on Evidence from Proteomics Analysis. Scientific Reports, 14, Article No. 23486. https://doi.org/10.1038/s41598-024-67337-7
[34]	Yang, M., Wu, W., Dong, N. and Li, M. (2026) 92-Plex Inflammatory Proteomic Signatures in Aqueous Humor of High Myopia and Candidate Biomarkers. Clinical Ophthalmology, 20, 1-12. https://doi.org/10.2147/opth.s614714
[35]	Zhu, M., Huang, Z., Li, M., Fang, Y., Du, Y., Lu, Y., et al. (2025) Proteomic Profiling Reveals ANGPTL7 Elevation in Aqueous Humor Linked to Intraocular Pressure Dysregulation in High Myopia. Journal of Proteome Research, 24, 6033-6044. https://doi.org/10.1021/acs.jproteome.5c00458
[36]	Wang, D., Wang, C., Hu, Z., Su, Y. and Jia, Z. (2025) A Preliminary Proteomic Analysis of Tear Fluid in Patients with High Myopia. BMC Ophthalmology, 25, Article No. 302. https://doi.org/10.1186/s12886-025-04129-1
[37]	Mérida, S., Návea, A., Desco, C., Celda, B., Pardo-Tendero, M., Morales-Tatay, J.M., et al. (2024) Glutathione and a Pool of Metabolites Partly Related to Oxidative Stress Are Associated with Low and High Myopia in an Altered Bioenergetic Environment. Antioxidants, 13, Article 539. https://doi.org/10.3390/antiox13050539
[38]	Huo, Q., Xu, Y., Wang, Y., Zhang, S., Liu, Z. and Li, J. (2025) Metabolomics Analysis of Aqueous Humor from Patients with High-Myopia Complicated Nuclear Cataract. Frontiers in Medicine, 12, Article 1454840. https://doi.org/10.3389/fmed.2025.1454840
[39]	Liu, X., Wu, Y., Liu, Y., Qian, W., Huang, L., Wu, Y., et al. (2025) UPLC-MS/MS-Based Serum Metabolomics Analysis for Comprehensive Pathological Myopia Profiling. Experimental Eye Research, 251, Article 110152. https://doi.org/10.1016/j.exer.2024.110152
[40]	Qi, Z., Qi, J., Zhang, Y., Wang, Y., Feng, Y., Yang, Z., et al. (2025) Plasma Metabolic Profile with Machine Learning Reveals Distinct Diagnostic and Biological Signatures for Pathologic Myopia. Advanced Science, 12, e05861. https://doi.org/10.1002/advs.202505861
[41]	Li, H., Du, Y., Cheng, K., Chen, Y., Wei, L., Pei, Y., et al. (2024) Gut Microbiota-Derived Indole-3-Acetic Acid Suppresses High Myopia Progression by Promoting Type I Collagen Synthesis. Cell Discovery, 10, Article No. 89. https://doi.org/10.1038/s41421-024-00709-5
[42]	Gu, X., Ruan, X., Yang, W., He, J., Tang, L., Niu, D., et al. (2025) Integrative Multi-Omics Identifies Coordinated Alterations in the Gut Microbiome and in Plasma and Aqueous Humor Metabolomes in High Myopic Cataract. Scientific Reports, 15, Article No. 39636. https://doi.org/10.1038/s41598-025-23265-8
[43]	Meng, J., Zhang, Y., Zhu, M., Du, Y., Yao, Y., Liu, S., et al. (2025) Single-Cell Profiling Reveals a Shared Proinflammatory Macrophage Signature across Multiple Organs in Myopia. Cell Discovery, 11, Article No. 97. https://doi.org/10.1038/s41421-025-00835-8
[44]	Belete, G.T., Zhou, L., Li, K.K., et al. (2024) Metabolomics Studies in Common Multifactorial Eye Disorders: A Review of Biomarker Discovery for Age-Related Macular Degeneration, Glaucoma, Diabetic Retinopathy and Myopia. Frontiers in Molecular Biosciences, 11, Article 1403844. https://doi.org/10.3389/fmolb.2024.1403844

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