Abstract
Development of myopia is associated with large-scale changes in ocular tissue gene expression. Although differential expression of coding genes underlying development of myopia has been a subject of intense investigation, the role of non-coding genes such as microRNAs in the development of myopia is largely unknown. In this study, we explored myopia-associated miRNA expression profiles in the retina and sclera of C57Bl/6J mice with experimentally induced myopia using microarray technology. We found a total of 53 differentially expressed miRNAs in the retina and no differences in miRNA expression in the sclera of C57BL/6J mice after 10 days of visual form deprivation, which induced -6.93 ± 2.44 D (p < 0.000001, n = 12) of myopia. We also identified their putative mRNA targets among mRNAs found to be differentially expressed in myopic retina and potential signaling pathways involved in the development of form-deprivation myopia using miRNA-mRNA interaction network analysis. Analysis of myopia-associated signaling pathways revealed that myopic response to visual form deprivation in the retina is regulated by a small number of highly integrated signaling pathways. Our findings highlighted that changes in microRNA expression are involved in the regulation of refractive eye development and predicted how they may be involved in the development of myopia by regulating retinal gene expression.
Highlights
Myopia is the most common vision disorder and a leading cause of visual impairment worldwide [1]
This profiling revealed that a total of 53 miRNAs were differentially expressed (FC ! 2.0; FDR-adjusted p < 0.05) in the myopic retina compared to the contralateral control retina, whereas no differentially expressed miRNAs were identified in the sclera (Fig 2; Table 1)
The majority of the differentially expressed miRNAs originated from different miRNA clusters, mmu-miR429-3p and mmu-miR-200a-5p belonged to the same cluster (MID < 5 kb) on chromosome 4 and were both up-regulated in myopic retina, while mmu-miR-145-5p and mmu-miR-143-3p localized within the same cluster (MID < 5 kb) on chromosome 18 and were both down-regulated in myopic retina (Table 1) [68]
Summary
Myopia is the most common vision disorder and a leading cause of visual impairment worldwide [1]. Optical defocus evokes a signaling cascade that originates in the retina, propagates through other ocular tissues (i.e., retinal pigment epithelium and choroid), and results in scleral wall remodeling with increased eye growth. This signaling is associated with large-scale changes in gene expression in all ocular tissues, which was extensively studied at the mRNA level in several animal models of myopia [10,11,12,13,14,15,16,17]. These studies established that modulation of gene expression plays an important role in refractive eye development, non-coding transcriptome changes underlying refractive eye development have been largely unexplored
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