Author: Haowen Xue
Artist: Naomi Chung
Editor: Hannah Walter
Myopia, a condition commonly known as “refractive error”, is caused by the focusing of light rays in front of the retina (instead of on it) due to the eyeball being too long. Nearly 1 in 5 teenagers are diagnosed as being myopic, and this is becoming an increasingly prevalent disorder globally. Therefore, it is important that we understand its basic mechanism and the ways to prevent the further progression of myopia. While it is obvious that genetics is a major factor in myopia pathogenesis, factors of epigenetics (the study of changes in phenotype due to changes in gene expression, rather than changes in the DNA base sequence) are also significant. This article will discuss how epigenetics may increase the risk of developing myopia.
Studies have revealed that epigenetics plays a critical pathogenic role in myopia progression. A recent paper has shown that more than fifteen gene loci (physical locations of genes on a chromosome) have been identified as being hotspots of DNA methylation in highly myopic people. DNA methylation is the process by which methyl groups are added to the DNA, causing transcription to be repressed. Some of these ‘hotspot’ loci include genes that regulate cell differentiation and growth factor signalling. The increased methylation in these particular regions results in more highly condensed DNA, which greatly reduces the access of transcription factors that initiate the transcription of these genes. It’s no wonder that as a result, the gene products (i.e. proteins produced from these genes that are involved in internal regulations) from these loci decreases greatly. For example, the increased methylation of SOD3 leads to misregulation of oxidative stress, which could induce oxidative damage to the eyes.
Other genes, such as MARK2 (which is vital in maintaining the movement of mitochondria in the retina and helps in proper neuronal function) and SP1 (which is crucial for corneal development) are also found hypermethylated, leading to increased refractive error and abnormal thinning of corneas due to a very low level of functional gene products. Additionally, based on investigations of children under the age of 12, other genes associated with myopia have been shown to have a CpG site with a reduction in methylation among myopic children. For example, the decrease in methylation on the CpG island of one of the semaphorin genes causes an elevated level of expression of SEMA5A, which has been significantly associated with myopia by inhibiting axon growth by retinal ganglion cells. This means that the length of neuronal fibres is reduced, inhibiting the retinal growth cones even in the presence of growth signalling molecules. Furthermore, previous studies identified that genes related to myopia could also be found in the brain, affecting neuronal development and signalling. It is possible that myopia is initiated by a signalling cascade involving the sensory retina, choroid, and retinal pigment epithelium that results in changes in scleral physiology, such as elongation of the eyeball.
It is therefore important to limit myopia progression by reducing gaps in our knowledge on the condition, and collecting data on both genetic and epigenetic risk factors. Hopefully, more research will be carried out to investigate the link between epigenetics and myopia, which may provide more information for the medical and public health sectors in early detection and therapeutic interventions.
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