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Updated: Mar 12, 2026
Inducement and Evaluation of a Murine Model of Experimental Myopia
Published on: January 22, 2019
Genome-Wide Scleral Micro- and Messenger-RNA Regulation During Myopia Development in the Mouse
Ravikanth Metlapally1, Han Na Park2, Ranjay Chakraborty3
1School of Optometry, University of California at Berkeley, Berkeley, California, United States.
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.
Insights
MicroRNAs (miRNAs) and messenger RNAs (mRNAs) in the sclera are differentially expressed in myopia, indicating their role in eye growth regulation. This finding supports miRNAs as potential therapeutic targets for myopia control.
Area of Science:
- Ophthalmology
- Genetics
- Molecular Biology
Background:
- MicroRNAs (miRNAs) are implicated in scleral remodeling during normal eye growth.
- miRNAs present potential therapeutic targets for managing myopia by modulating scleral matrix remodeling.
Purpose of the Study:
- To investigate genome-wide miRNA and messenger RNA (mRNA) scleral profiles in myopic versus control mouse eyes.
- To explore the potential of miRNAs as therapeutic targets for myopia prevention or retardation.
Main Methods:
- Unilateral form-deprivation (FD) was induced in C57BL/6J mice (P28) for 2 weeks.
- Refractive error and axial length were measured; scleral RNA was analyzed via microarray.
- Differential gene expression was confirmed using quantitative PCR.
Main Results:
- FD eyes exhibited myopic shifts (-2.02 ± 0.47 D).
- 54 miRNAs and 261 mRNAs were differentially expressed in FD eyes compared to controls (fold-change >1.25, P < 0.05).
- Key ontologies included intermediate filament organization and phototransduction; Let-7a, miR-16-2, Smok4a, Prph2, and Gnat1 showed differential expression.
Conclusions:
- Differential expression of scleral miRNAs and mRNAs is linked to myopia.
- These findings support the involvement of miRNAs in regulating eye growth.
- The observed small fold-changes suggest a tightly regulated scleral gene expression mechanism.
