Abstract
PurposeA recent meta-analysis revealed PAX6 as a risk gene for myopia. There is a link between PAX6 and HOXA9. Furthermore, HOXA9 has been reported to activate TGF-β that is a risk factor for myopia. We speculate HOXA9 may participate in myopia development.MethodsThe Singapore GUSTO birth cohort provides data on children’s cycloplegic refraction measured at age of 3 years and their methylation profile based on the umbilical cord DNA. The HOXA9 expression levels were measured in the eyes of mono-ocular form deprivation myopia in mice. The plasmid with the mouse HOXA9 cDNA was constructed and then transfected to mouse primary retinal pigment epithelial (RPE) cells. The expression levels of myopia-related genes and cell proliferation were measured in the HOXA9-overexpressed RPE cells.ResultsA total of 519 children had data on methylation profile and cycloplegic refraction. The mean spherical equivalent refraction (SE) was 0.90D. Among 8 SE outliers (worse than -2D), 7 children had HOXA9 hypomethylation. The HOXA9 levels in the retina of myopic eyes was 2.65-fold (p = 0.029; paired t-test) higher than the uncovered fellow eyes. When HOXA9 was over-expressed in the RPE cells, TGF-β, MMP2, FGF2 and IGF1R expression levels were dose-dependently increased by HOXA9. However, over-expression of HOXA9 had no significant influence on IGF1 or HGF expression. In addition, HOXA9 also increased RPE proliferation.ConclusionBased on the human, animal and cellular data, the transcription factor HOXA9 may promote the expression of pro-myopia genes and RPE proliferation, which eventually contribute to myopia development.
Highlights
Myopia is a common eye condition worldwide, and its prevalence varies widely among populations and ages [1,2,3]
When HOXA9 was over-expressed in the retinal pigment epithelial (RPE) cells, transforming growth factor-β (TGF-β), MMP2, FGF2 and IGF1R expression levels were dose-dependently increased by HOXA9
Based on the human, animal and cellular data, the transcription factor HOXA9 may promote the expression of pro-myopia genes and RPE proliferation, which eventually contribute to myopia development
Summary
Myopia is a common eye condition worldwide, and its prevalence varies widely among populations and ages [1,2,3]. Both genetic and environmental factors contribute to the development of myopia [4]. Several myopia susceptibility genes have been reported based on genetic association studies as well as gene expression studies [5,6,7]. Data from meta-analysis of genome-wide association studies further reported newly identified genetic loci [8,9,10]. Several environmental risk factors were reported to be associated with myopia.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
