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Ravi Metlapally, Hanna Park, Kevin Wang, Christopher C Tan, Jacob G Light, Machelle T Pardue, Christine Wildsoet; Genome-wide scleral micro- and messenger-RNA profiling in the mouse myopia model. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3588.
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miRNAs (micro-RNAs) play critical roles in normal physiological as well as disease processes. Recent studies implicated miRNAs in scleral remodeling and normal ocular growth. Through the modulation of scleral extracellular matrix genes, miRNAs have potential to be therapeutic scleral targets for myopia prevention/retardation strategies. As a first step, genome-wide miRNA and mRNA (messenger-RNA) expression profiles in myopic and control eyes of mice were studied using microarray analyses.
C57BL/6J mice (n=7, P28), reared under a 12 hr light-dark cycle, were form-deprived (FD) unilaterally for 2 weeks. Refractive error and axial length measurements were made using photorefraction and 1310nm SD-OCT. Scleral RNA samples from FD and control eyes were processed for mirBASE version 19 miRNA (1279 miRNAs) and Affymetrix GeneChip Gene 2.0 ST (>28000 mRNAs) microarrays. Statistical analyses were performed using the NIA (National Institute on Aging) Array Analysis Tool. Briefly, raw data were background subtracted, log-transformed, normalized and average intensities as well as fold differences calculated. Group comparisons were made using ANOVA. Functional biological pathways were identified using WebGestalt software.
FD eyes showed myopic shifts in refractive error (mean interocular difference: -2.90 +/- 0.86D, p<0.05). Comparison of scleral RNA profiles for FD and control eyes revealed a total of 54 miRNAs and 261 mRNAs differentially expressed (fold change >1.25 fold in either direction, max FC=1.63 for miRNA, 2.7 for mRNA) (p<0.05, min p=0.0001). miRNAs of the let-7 family, previously implicated in matrix remodeling in other tissues, were upregulated in eyes developing axial myopia. Notable statistically significant (p<0.05) pathways showing over-representation of genes included intermediate filament organization, scaffold protein binding, detection of stimuli, calcium ion, G-protein, and photo-transduction pathways.
A number of scleral mi- and m-RNAs showed differential expression linked to myopia in the mouse model, further supporting the involvement of miRNAs in scleral remodeling. The observed general trend of relatively small fold changes is perhaps indicative of a tightly controlled regulatory mechanism for scleral gene expression. Further validation and molecular studies aimed at understanding specific mechanisms related to myopia are planned.
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