Integrative Transcriptome and Proteome Analyses Elucidate the Mechanism of Lens-Induced Myopia in Mice

Overview

Journal Invest Ophthalmol Vis Sci

Specialty Ophthalmology

Date 2023 Oct 11

PMID 37819745

Authors

Shunmei Ji

Lin Ye

Jiayue Yuan

Qianhong Feng

Jinhui Dai

Affiliations

Soon will be listed here.

Abstract

Purpose: The purpose of this study was to investigate the underlying molecular mechanism of lens-induced myopia (LIM) through transcriptome and proteome analyses with a modified mouse myopia model.

Methods: Four-week-old C57BL/6J mice were treated with a homemade newly designed -25 diopter (D) lens mounting by a 3D printing pen before right eyes for 4 weeks. Refraction (RE) and axial dimensions were measured every 2 weeks. Retinas were analyzed by RNA-sequencing and data-independent acquisition liquid chromatography tandem mass spectrometry. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation, and STRING databases were used to identify significantly affected pathways in transcriptomic and proteomic data sets. Western blot was used to detect the expression of specific proteins.

Results: The modified model was accessible and efficient. Mice displayed a significant myopic shift (approximately 8 D) following 4 weeks' of lens treatment. Through transcriptomics and proteomics analysis, we elucidated 175 differently expressed genes (DEGs) and 646 differentially expressed proteins (DEPs) between binoculus. The transcriptomic and proteomic data showed a low correlation. Going over the mRNA protein matches, insulin like growth factor 2 mRNA binding protein 1 (Igf2bp1) was found to be a convincing biomarker of LIM, which was confirmed by Western blot. RNA-seq and proteome profiling confirmed that these two "omics" data sets complemented one another in KEGG pathways annovation. Among these, metabolic and human diseases pathways were considered to be correlated with the LIM forming process.

Conclusions: The newly constructed LIM model provides a useful tool for future myopia research. Combining transcriptomic and proteomic analysis may potentially brighten the prospects of novel therapeutic targets for patients with myopia.

Citing Articles

Meta-analysis of retinal transcriptome profiling studies in animal models of myopia.

Palumaa T, Balamurugan S, Pardue M Front Med (Lausanne). 2025; 11:1479891.

PMID: 39876870 PMC: 11772478. DOI: 10.3389/fmed.2024.1479891.

The impact of light properties on ocular growth and myopia development.

Chen Y, Tsai T, Liu Y, Lin H, Wang I Taiwan J Ophthalmol. 2024; 14(2):143-150.

PMID: 39027063 PMC: 11253990. DOI: 10.4103/tjo.TJO-D-24-00031.

References

Siegwart Jr J, Norton T . Binocular lens treatment in tree shrews: Effect of age and comparison of plus lens wear with recovery from minus lens-induced myopia. Exp Eye Res. 2010; 91(5):660-9. PMC: 2962680. DOI: 10.1016/j.exer.2010.08.010. View

Bian J, Sze Y, Tse D, To C, McFadden S, Lam C . SWATH Based Quantitative Proteomics Reveals Significant Lipid Metabolism in Early Myopic Guinea Pig Retina. Int J Mol Sci. 2021; 22(9). PMC: 8124159. DOI: 10.3390/ijms22094721. View

Zhao F, Li Q, Chen W, Zhu H, Zhou D, Reinach P . Dysfunction of VIPR2 leads to myopia in humans and mice. J Med Genet. 2020; 59(1):88-100. DOI: 10.1136/jmedgenet-2020-107220. View

Verhoeven V, Wong K, Buitendijk G, Hofman A, Vingerling J, Klaver C . Visual consequences of refractive errors in the general population. Ophthalmology. 2014; 122(1):101-9. DOI: 10.1016/j.ophtha.2014.07.030. View

Love M, Huber W, Anders S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15(12):550. PMC: 4302049. DOI: 10.1186/s13059-014-0550-8. View

Lan T, Jiang S, Zhang J, Weng Q, Yu Y, Li H . Breviscapine alleviates NASH by inhibiting TGF-β-activated kinase 1-dependent signaling. Hepatology. 2021; 76(1):155-171. PMC: 9299589. DOI: 10.1002/hep.32221. View

Verhoeven V, Hysi P, Wojciechowski R, Fan Q, Guggenheim J, Hohn R . Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia. Nat Genet. 2013; 45(3):314-8. PMC: 3740568. DOI: 10.1038/ng.2554. View

Gu Y, Xu B, Feng C, Ni Y, Wu Q, Du C . A Head-Mounted Spectacle Frame for the Study of Mouse Lens-Induced Myopia. J Ophthalmol. 2016; 2016:8497278. PMC: 4745417. DOI: 10.1155/2016/8497278. View

Grochowski E, Pietrowska K, Kowalczyk T, Mariak Z, Kretowski A, Ciborowski M . Omics in Myopia. J Clin Med. 2020; 9(11). PMC: 7692398. DOI: 10.3390/jcm9113464. View

10.

McMillan J . Spectrum of Darkness, Agent of Light: Myopia, Keratoconus, Ocular Surface Disease, and Evidence for a Profoundly Vitamin D-dependent Eye. Cureus. 2018; 10(6):e2744. PMC: 6075645. DOI: 10.7759/cureus.2744. View

11.

Jiang X, Kurihara T, Kunimi H, Miyauchi M, Ikeda S, Mori K . A highly efficient murine model of experimental myopia. Sci Rep. 2018; 8(1):2026. PMC: 5794929. DOI: 10.1038/s41598-018-20272-w. View

12.

Barathi V, Boopathi V, Yap E, Beuerman R . Two models of experimental myopia in the mouse. Vision Res. 2008; 48(7):904-16. DOI: 10.1016/j.visres.2008.01.004. View

13.

Faulkner A, Kim M, Iuvone P, Pardue M . Head-mounted goggles for murine form deprivation myopia. J Neurosci Methods. 2006; 161(1):96-100. DOI: 10.1016/j.jneumeth.2006.10.011. View

14.

Tkatchenko T, Shen Y, Tkatchenko A . Mouse experimental myopia has features of primate myopia. Invest Ophthalmol Vis Sci. 2009; 51(3):1297-303. PMC: 2829371. DOI: 10.1167/iovs.09-4153. View

15.

Tkatchenko T, Troilo D, Benavente-Perez A, Tkatchenko A . Gene expression in response to optical defocus of opposite signs reveals bidirectional mechanism of visually guided eye growth. PLoS Biol. 2018; 16(10):e2006021. PMC: 6177118. DOI: 10.1371/journal.pbio.2006021. View

16.

Zhou X, Pardue M, Iuvone P, Qu J . Dopamine signaling and myopia development: What are the key challenges. Prog Retin Eye Res. 2017; 61:60-71. PMC: 5653403. DOI: 10.1016/j.preteyeres.2017.06.003. View

17.

Shan S, Wang P, Cheung J, Yu F, Zheng H, Luo S . Transcriptional profiling of the chick retina identifies down-regulation of and genes during early lens-induced myopia. Mol Omics. 2022; 18(5):449-459. DOI: 10.1039/d1mo00407g. View

18.

Pardue M, Stone R, Iuvone P . Investigating mechanisms of myopia in mice. Exp Eye Res. 2013; 114:96-105. PMC: 3898884. DOI: 10.1016/j.exer.2012.12.014. View

19.

Dong M, Wang S, Xu F, Xiao G, Bai J, Wang J . Integrative transcriptome and proteome analyses of Trichoderma longibrachiatum LC and its cellulase hyper-producing mutants generated by heavy ion mutagenesis reveal the key genes involved in cellulolytic enzymes regulation. Biotechnol Biofuels Bioprod. 2022; 15(1):63. PMC: 9166314. DOI: 10.1186/s13068-022-02161-7. View

20.

Li J, Jiang D, Xiao X, Li S, Jia X, Sun W . Evaluation of 12 myopia-associated genes in Chinese patients with high myopia. Invest Ophthalmol Vis Sci. 2015; 56(2):722-9. DOI: 10.1167/iovs.14-14880. View