Genome-wide analysis of microRNA-mRNA gene regulatory networks reveals widespread involvement of microRNAs in visually guided eye emmetropization and myopia [mRNA retina]

During postnatal development, the optical geometry of the eye is refined through a process called emmetropization. During eye emmetropization, optical defocus triggers a signaling cascade that originates in the retina, propagates across other ocular tissues and results in scleral wall remodeling. This signaling is associated with large-scale changes in gene expression, which was extensively studied at the mRNA level. Although several studies investigated the role of non-coding RNAs in eye emmetropization, the role of microRNAs (miRNAs) and other non-coding RNAs remains poorly understood. We performed a genome-wide analysis of the miRNA-mRNA gene regulatory networks underlying optical-defocus-induced myopia using massive parallel RNA sequencing (RNA-seq). Our analysis revealed a widespread involvement of miRNAs in optical defocus perception and visually guided eye emmetropization underlying myopia development. We found that a relatively small number of miRNAs (39 miRNAs total) regulate expression of over 450 mRNAs, or 59% of all mRNAs differentially expressed in the eyes of mice with optical-defocus-induced myopia. MiRNAs were also found to be involved in the regulation of the absolute majority of the biological processes and signaling pathways underlying visually guided eye emmetropization and myopia.