Abstract
Purpose
Increasing evidence suggests myopia is not a simple refractive error, many other factors might also be involved. Here, we assessed myopic and normal corneas’ gene expression profiles to identify possible diagnostic and therapeutic biomarkers for myopia.
Materials and methods
We obtained the expression profile of ten patients and seven normal control samples from the GSE112155 and GSE151631 datasets based on the Gene Expression Omnibus (GEO) database. We used the “limma” R package to determine the differentially expressed genes (DEGs) between myopic and normal corneas. Weighted gene co-expression network analysis (WGCNA) was used to identify critical co-expressed modules related to myopia, and enrichment analyses were used to annotate the function of genes encompassed in the compulsory module. We also validated these findings in two external datasets (GSE24641 and GSE136701).
Results
We identified that the DEGs were significantly enriched in ultraviolet (UV) response, TNF-α signaling via NFκB, Angiogenesis, Myogenesis pathways, etc. We used 2095 genes to construct the co-expression gene modules and found five interesting modules because the eigengene expression of these modules was significantly differentially expressed between myopic and normal corneas. Notably, the enrichment analysis found that the genes encompassed in lightgreen module were significantly enriched in immune-related pathways. These findings were proved by subsequent analysis based on Xcell software. We found the component of B cells, CD4+ memory T cells, CD8+ central memory T cells, plasmacytoid dendritic cells, T helper 2 (Th2) cells, regulatory T cells (Tregs), etc. were significantly increased in myopic corneas, while CD8+ T cells, CD4+ T central memory cells, natural killer T (NKT) cells, and T helper 1 (Th1) cells were significantly decreased.
Conclusion
Our findings identified some markers that might detect diagnosis and treatment for myopia from cornea aspect. Future studies are warranted to verify the functional role of immune-related pathways in cornea during the pathogenesis or progression of myopia.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Holden BA, Fricke TR, Wilson DA, Jong M, Naidoo KS, Sankaridurg P, et al. Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050. Ophthalmology. 2016;123:1036–42.
Carney LG, Mainstone JC, Henderson BA. Corneal topography and myopia. A cross-sectional study. Invest Ophthalmol Vis Sci. 1997;38:311–20.
Horner DG, Soni PS, Vyas N, Himebaugh NL. Longitudinal changes in corneal asphericity in myopia. Optom Vis Sci. 2000;77:198–203.
Zhang Q, Guo X, Xiao X, Jia X, Li S, Hejtmancik JF. A new locus for autosomal dominant high myopia maps to 4q22-q27 between D4S1578 and D4S1612. Mol Vis. 2005;11:554–60.
Zhang Q, Guo X, Xiao X, Jia X, Li S, Hejtmancik JF. Novel locus for X linked recessive high myopia maps to Xq23-q25 but outside MYP1. J Med Genet. 2006;43:e20.
Shi Y, Li Y, Zhang D, Zhang H, Li Y, Lu F, et al. Exome sequencing identifies ZNF644 mutations in high myopia. PLoS Genet. 2011;7:e1002084.
Tran-Viet KN, Powell C, Barathi VA, Klemm T, Maurer-Stroh S, Limviphuvadh V, et al. Mutations in SCO2 are associated with autosomal-dominant high-grade myopia. Am J Hum Genet. 2013;92:820–6.
Guo H, Jin X, Zhu T, Wang T, Tong P, Tian L, et al. SLC39A5 mutations interfering with the BMP/TGF-beta pathway in non-syndromic high myopia. J Med Genet. 2014;51:518–25.
Zhao F, Wu J, Xue A, Su Y, Wang X, Lu X, et al. Exome sequencing reveals CCDC111 mutation associated with high myopia. Hum Genet. 2013;132:913–21.
Guo H, Tong P, Liu Y, Xia L, Wang T, Tian Q, et al. Mutations of P4HA2 encoding prolyl 4-hydroxylase 2 are associated with nonsyndromic high myopia. Genet Med. 2015;17:300–6.
Riddell N, Giummarra L, Hall NE, Crewther SG. Bidirectional expression of metabolic, structural, and immune pathways in early myopia and hyperopia. Front Neurosci. 2016;10:390.
Lazuk AV, Slepova OS, Tarutta EP. Antibodies to collagen in patients with progressive myopia. In: Tokoro T, editor. Myopia updates: Proceedings of the 6th International Conference on Myopia. Tokyo, Japan: Springer; 1998. p. 120–3.
Yuan J, Wu S, Wang Y, Pan S, Wang P, Cheng L. Inflammatory cytokines in highly myopic eyes. Sci Rep. 2019;9:3517.
Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43:e47.
Zhang Y, Parmigiani G, Johnson WE. ComBat-seq: batch effect adjustment for RNA-seq count data. NAR Genom Bioinform. 2020;2:lqaa078.
Langfelder P, Horvath S. WGCNA: an R package for weighted correlation network analysis. BMC Bioinforma. 2008;9:559.
Zhang C, Peng L, Zhang Y, Liu Z, Li W, Chen S, et al. The identification of key genes and pathways in hepatocellular carcinoma by bioinformatics analysis of high-throughput data. Med Oncol. 2017;34:101.
Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012;16:284–7.
Aran D, Hu Z, Butte AJ. xCell: digitally portraying the tissue cellular heterogeneity landscape. Genome Biol. 2017;18:220.
Chou WC, Cheng AL, Brotto M, Chuang CY. Visual gene-network analysis reveals the cancer gene co-expression in human endometrial cancer. BMC Genomics. 2014;15:300.
Kawai T, Akira S. Innate immune recognition of viral infection. Nat Immunol. 2006;7:131–7.
Kim S, Shin S, Hyun B, Kong H, Han S, Lee A, et al. Immunomodulatory effects of dioscoreae rhizome against inflammation through suppressed production of cytokines via inhibition of the NF-κB pathway. Immune Netw. 2012;12:181–8.
Fledelius HC. Is myopia getting more frequent? A cross-sectional study of 1416 Danes aged 16 years+. Acta Ophthalmol. 1983;61:545–59.
Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. 2011;11:98–107.
Palejwala NV, Walia HS, Yeh S. Ocular manifestations of systemic lupus erythematosus: a review of the literature. Autoimmune Dis. 2012;2012:290898.
Nguyen QD, Foster CS. Saving the vision of children with juvenile rheumatoid arthritis-associated uveitis. JAMA. 1998;280:1133–4.
Päivönsalo-Hietanen T, Tuominen J, Saari KM. Uveitis in children: population-based study in Finland. Acta Ophthalmol. 2000;78:84–8.
Kesen MR, Setlur V, Goldstein DA. Juvenile idiopathic arthritis-related uveitis. Int Ophthalmol Clin. 2008;48:21–38.
Chen W, Zhao B, Jiang R, Zhang R, Wang Y, Wu H, et al. Cytokine expression profile in aqueous humor and sera of patients with acute anterior uveitis. Curr Mol Med. 2015;15:543–9.
Lin HJ, Wei CC, Chang CY, Chen TH, Hsu YA, Hsieh YC, et al. Role of chronic inflammation in myopia progression: clinical evidence and experimental validation. EBioMedicine. 2016;10:269–81.
Author information
Authors and Affiliations
Contributions
YN, LW, and CL performed bioinformatics analysis. YN and JZ designed the research study. YN prepared the paper drafting. ZL, JY and JZ performed paper editing. All authors contributed to the article and approved the submitted version.
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Ni, Y., Wang, L., Liu, C. et al. Gene expression profile analyses to identify potential biomarkers for myopia. Eye 37, 1264–1270 (2023). https://doi.org/10.1038/s41433-022-02013-6
Received:
Revised:
Accepted:
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41433-022-02013-6
This article is cited by
-
Inflammation and Immune Pathways in Myopia: An Overview on Pathomechanisms and Treatment Prospects
Clinical Reviews in Allergy & Immunology (2025)
-
Comparisons of the protein expressions between high myopia and moderate myopia on the anterior corneal stroma in human
Graefe's Archive for Clinical and Experimental Ophthalmology (2023)
