Genome-Wide Scleral Micro- and Messenger-RNA Regulation During Myopia Development in the Mouse

Overview

Journal Invest Ophthalmol Vis Sci

Specialty Ophthalmology

Date 2016 Nov 11

PMID 27832275

Citations 14

Authors

Ravikanth Metlapally

Han Na Park

Ranjay Chakraborty

Kevin K Wang

Christopher C Tan

Jacob G Light

Machelle T Pardue

Christine F Wildsoet

Affiliations

Soon will be listed here.

Abstract

Purpose: MicroRNA (miRNAs) have been previously implicated in scleral remodeling in normal eye growth. They have the potential to be therapeutic targets for prevention/retardation of exaggerated eye growth in myopia by modulating scleral matrix remodeling. To explore this potential, genome-wide miRNA and messenger RNA (mRNA) scleral profiles in myopic and control eyes from mice were studied.

Methods: C57BL/6J mice (n = 7; P28) reared under a 12L:12D cycle were form-deprived (FD) unilaterally for 2 weeks. Refractive error and axial length changes were measured using photorefraction and 1310-nm spectral-domain optical coherence tomography, respectively. Scleral RNA samples from FD and fellow control eyes were processed for microarray assay. Statistical analyses were performed using National Institute of Aging array analysis tool; group comparisons were made using ANOVA, and gene ontologies were identified using software available on the Web. Findings were confirmed using quantitative PCR in a separate group of mice (n = 7).

Results: Form-deprived eyes showed myopic shifts in refractive error (-2.02 ± 0.47 D; P < 0.01). Comparison of the scleral RNA profiles of test eyes with those of control eyes revealed 54 differentially expressed miRNAs and 261 mRNAs fold-change >1.25 (maximum fold change = 1.63 and 2.7 for miRNAs and mRNAs, respectively) (P < 0.05; minimum, P = 0.0001). Significant ontologies showing gene over-representation (P < 0.05) included intermediate filament organization, scaffold protein binding, detection of stimuli, calcium ion, G protein, and phototransduction. Significant differential expression of Let-7a and miR-16-2, and Smok4a, Prph2, and Gnat1 were confirmed.

Conclusions: Scleral mi- and mRNAs showed differential expression linked to myopia, supporting the involvement of miRNAs in eye growth regulation. The observed general trend of relatively small fold-changes suggests a tightly controlled, regulatory mechanism for scleral gene expression.

Citing Articles

Applications of Genomics and Transcriptomics in Precision Medicine for Myopia Control or Prevention.

Jiang L, Goh D, Koh J, Chan X, Brennan N, Barathi V Biomolecules. 2023; 13(3).

PMID: 36979429 PMC: 10046175. DOI: 10.3390/biom13030494.

Differential methylation of microRNA encoding genes may contribute to high myopia.

Swierkowska J, Vishweswaraiah S, Mrugacz M, Radhakrishna U, Gajecka M Front Genet. 2023; 13:1089784.

PMID: 36685896 PMC: 9847511. DOI: 10.3389/fgene.2022.1089784.

Scleral remodeling in myopia development.

Yu Q, Zhou J Int J Ophthalmol. 2022; 15(3):510-514.

PMID: 35310066 PMC: 8907044. DOI: 10.18240/ijo.2022.03.21.

MicroRNA-1 Expression and Function in (Acari: Ixodidae) Ticks.

Luo J, Ren Q, Liu W, Qiu X, Zhang G, Tan Y Front Physiol. 2021; 12:596289.

PMID: 33897444 PMC: 8061306. DOI: 10.3389/fphys.2021.596289.

RNA-seq and GSEA identifies suppression of ligand-gated chloride efflux channels as the major gene pathway contributing to form deprivation myopia.

Vocale L, Crewther S, Riddell N, Hall N, Murphy M, Crewther D Sci Rep. 2021; 11(1):5280.

PMID: 33674625 PMC: 7935918. DOI: 10.1038/s41598-021-84338-y.

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