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DNA Methylation Linked to Early-Onset Myopia

In a recent study, CpG site-specific methylation was found to be significantly associated with the development of myopia in three year old children.


Image source: https://www.clinicabaviera.com/blog/wp-content/uploads/2017/11/iStock-494711582-300x199.jpg

Myopia, also known as nearsightedness, is caused by changes in the shape of the eye. As it elongates, light refraction in the eye alters such that images are focused in front of the retina, rather than directly on top of it as observed in normal vision. This translates to blurry, out of focus images when viewing objects that are further away.


Myopia is a very common disorder that affects over 30% of Canadians and has many possible genetic and environmental factors. These include ethnicity, the presence of myopia in one or both parents, and time spent outdoors. Another interesting risk factor is the age at which myopia is developed. In children that develop myopia at a very young age, the rate of myopia progression is accelerated and the overall severity of myopia at stabilization is increased.


A recent study published in the journal PLOS ONE aimed to investigate the potential role of DNA methylation in the development of early-onset myopia. To do this, the researchers followed children from birth to 3 years of age. At birth, umbilical samples were retrieved and a genome-wide DNA methylation profile was performed. Then at 3 years of age, eye measurements were taken to diagnose myopia. The two sets of data were then compared to determine if there was a pattern in the DNA methylation profile of children that developed early-onset myopia.


Upon comparing the DNA methylation and eye measurement data, the researchers identified five CpG sites that had significant associations with the development of early onset myopia. These included two CpG sites in intergenic regions 8p23 and 12q23.2, as well as sites in genes that encode Fibrinogen B beta (FGB), PQ-loop repeat-containing protein 1 (PQLC1), and keratin 12 (KRT12).



Statistically significant DNA methylation sites in myopic vs control children. Image source: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214791

The researchers then went on to study the expression of genes ADP Ribosylation Factor Like GTPase 1 (ARL1), FGB, PQLC1, and KRT12 in adult and fetal ocular tissue, as well as in a myopic mouse model. Three of the genes were expressed in human fetal ocular tissue (ARL1, KRT12, and PQLC1). The genes PQLC1 and KRT12 were also expressed in the mouse myopia model. Taken together, these results suggest that several of the genes identified in the first experiment are actually associated with eye function.


More importantly, the results of this study identify potential biomarkers of early-onset myopia, which as the researchers suggest, may possibly be used to predict outcomes in the eye so that the progression of myopia and development of more severe eye diseases associated with early-onset myopia can be tracked and treated efficiently.

Sources:

Recko, M., & Stahl, E. D. (2015). Childhood myopia: epidemiology, risk factors, and prevention. Missouri Medicine, 112(2), 116.

Seow, W. J., Ngo, C. S., Pan, H., Barathi, V. A., Tompson, S. W., Whisenhunt, K. N., ... & Young, T. L. (2019). In-utero epigenetic factors are associated with early-onset myopia in young children. PLOS ONE, 14(5), e0214791.

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