Abstract: As a complex disease, myopia is the most common eye disease worldwide. Many myopia susceptibility genes or variants have been successfully identified in the past years by genome-wide genetic association studies (GWAS), which focus mainly on the single-nucleotide polymorphisms. Little attention has been paid to examine the role of copy number variations (CNVs) in refractive error and myopia. This study adopted a systematic strategy to investigate the role of CNVs in high myopia. In the discovery phase, a pilot GWAS suggests putative CNVs for follow-up. Multiplex ligation-dependent probe amplification was then used to quantify the copy number of 89 CNV segments in 737 case-control samples in the second phase and then 24 top-ranking CNVs in a second group of 1,029 case-control samples in the final validation phase. This validation phase identified 22 significant CNVs. Further work is needed to examine the role of these few CNVs in myopia development.

Abstract: Myopia and astigmatism, two common refractive errors frequently co-exist, are degrading vision at all working distances in populations worldwide. Eyeballs having high degrees of myopia and astigmatism are known to exhibit abnormal eye shape at the anterior and posterior eye segments, but whether the outer coats of these abnormal eyeballs, cornea anteriorly and sclera posteriorly, are regulated by region-specific molecular mechanism remains unclear. Here we presented the changes in eye shape and mRNA expression levels of three genes (MMP2, TIMP2, and TGFB2), all known to participate in extracellular matrix organization, at five regions of the cornea and sclera in chickens developing high myopia and astigmatism induced by form deprivation. Our results showed that, compared to normal chicks, the highly myopic-astigmatic chicks had significantly astigmatic cornea, deeper anterior chamber, longer axial length, and higher expressions of all three genes in the superior sclera. These results imply that local molecular mechanism may manipulate the eye’s structural remodeling across the globe during refractive eye growth.