Form Deprivation-induced Myopia is Associated with DNA Methylation in the Promoter of CollagenIα1 Gene in Sclera

Abstract

Purpose: : To explore whether FDM (form deprivation myopia) induce DNA methylation in the promoter of collagen I α1 gene in mouse sclera.

Methods: : C57BL/6 mice (23 days, male) were divided into three groups randomly: (a) MD (Monocular form deprivation) group: mice were treated with diffuser worn on one eye for 28 days; (b) MD/Recovery group: mice were treated with diffusers for 28 days, but diffusers were removed for 7 days after 28 days of form deprivation; (c) Normal control groups: mice were not received any treatment for 35days, the same days of visual experience as the MD/Recovery mice. At the end of the treatment period, the refraction was measured by eccentric infrared photorefraction (EIR),ocular dimensions by customized optical coherence tomography (OCT), and corneal radius of curvature by modified keratometry. To analyze DNA methylation state, genome DNA were isolated from two sclera of mouse eyes in each group. After bisulfite conversion of DNA, methylation state of the promoter of collagen I α1 gene was determined by bisulfite DNA sequencing.

Results: : After MD for 28 days, the treated eyes showed significant myopic shift compared with their fellow eyes (P<0.05); the myopic shift in form deprived eye was correlated with the increase in vitreous chamber depth and axial length (P<0.05). Interestingly, the promoter region of collagen Iα1 was more frequently methylated in the deprived eyes than that in normal control eyes (P=0.038). The relative myopia shift was rapidly recovered to the level of the fellow and normal control eyes at 7 days after removal of the diffuser. Correlated with refractive shift, DNA methylation in the promoter of collagen Iα1 gene also reduced in the recovered eyes compared to the form deprived eyes (P=0.011), leading to no difference in DNA methylation of the among the recovery, fellow and normal control eyes.

Conclusions: : FDM induces myopic shift and enhanced DNA methylation in CpG island of collagen Iα1 promoter, which may in part contribute to altered collagen expression and development of myopia.

Keywords: myopia • genetics • sclera