HOXA9 is a novel myopia risk gene.

Area of Science:

• Ophthalmology
• Genetics
• Developmental Biology

Background:

• Myopia is a growing global health concern.
• PAX6 is a known risk gene for myopia.
• HOXA9 is linked to PAX6 and activates TGF-β, a myopia risk factor.

Purpose of the Study:

• To investigate the role of HOXA9 in myopia development.
• To examine the association between HOXA9 methylation and refractive error in children.
• To assess HOXA9 expression in mouse myopia models and its effect on retinal pigment epithelial (RPE) cells.

Main Methods:

• Analysis of umbilical cord DNA methylation and refractive error data from the Singapore GUSTO birth cohort (n=519).
• Measurement of HOXA9 expression in mouse eyes with experimentally induced myopia.
• In vitro study involving HOXA9 overexpression in mouse RPE cells to assess gene expression and proliferation.

Main Results:

• HOXA9 hypomethylation was observed in 7 out of 8 outlier myopia cases.
• HOXA9 levels were significantly higher in the retinas of myopic eyes compared to fellow eyes in mice.
• Overexpression of HOXA9 in RPE cells increased expression of myopia-related genes (TGF-β, MMP2, FGF2, IGF1R) and enhanced cell proliferation.

Conclusions:

• The transcription factor HOXA9 is implicated in myopia development.
• HOXA9 may promote myopia by upregulating pro-myopia genes and increasing RPE cell proliferation.
• These findings highlight HOXA9 as a potential therapeutic target for myopia.