Genome-wide scleral micro-and messenger-RNA regulation during myopia development in the mouse

MicroRNAs (miRNAs) are small noncoding molecules that play pivotal roles in cell signaling through regulation of gene expression, specifically, by pairing with complementary messenger RNA (mRNA) sequences to either suppress translation or degrade mRNA.1–3 It is now recognized that they play crucial roles in normal physiological and pathologic processes, both in nonocular and in ocular tissues.4,5 Previous studies that focused on the human ocular scleraimplicated miRNAs in normal ocular growth (axial elongation), with samples from very young, rapidly growing eyes, showing differential expression compared to those from adult (assumed) stable eyes. Some of the differentially expressed miRNAs could be linked to extracellular matrix remodeling pathways, making them potential targets for preventing or slowing the progression of myopia, which is largely a product of active scleral extracellular remodeling and thinning.6 As the first step in exploring the potential of miRNAs as therapeutic targets for myopia control, this study sought to understand their role in the scleral changes underlying myopia. We hypothesized that myopia development, when ocular axial elongation (“growth”) is exaggerated, is directly linked to differential regulation of scleral miRNAs. This study used a mouse model of myopia, which has distinct advantages over other animal models of myopia in that the mouse possesses a well-characterized genome and a short gestational period with large litter sizes.7 In the context of myopia, visual FD has been shown to induce myopic shifts in refractive errorby a number of different research laboratories.7–15 The mouse also has a fibrous sclera, like other mammals and primates.16,17 In this study, myopia was induced in young mice with short-term FD, and after the expected refractive errorand ocular dimensional changes were confirmed, genome-wide expression profiling of mi- and mRNAs of scleral tissue was undertaken using microarray analyses, and gene ontology/bioinformatic analyses coupled with validation experiments, using quantitative PCR. Briefly, this study revealed differentially expressed mi- and mRNAs linked to myopia, implicating miRNAs and specific signaling pathways in scleral extracellular matrix remodeling and eye growth regulation.