Myopia, also known as short-sightedness, is a refractive error defined as an optical condition where parallel light rays entering the eye are focussed before the retina, resulting in blurred image. Refractive error is measured in dioptres (D) and myopia is recorded using a negative sign. Optical correction of this refractive error can be done with spectacles, contact lenses and surgical procedures such as photorefractive keratectomy. People with myopia are usually classified into two groups, low to moderate myopia (0.00D to -6.00D) or high/pathological myopia (greater than -6.00D). High myopia is also known as pathological myopia because it is often associated with sight threatening ocular conditions such as retinal detachment, macular degeneration, and glaucoma (Fredrick, 2002). Also systemic findings of many genetic syndromes such as Marfan and Stickler syndromes have myopia as consistent feature (Terri et al., 2004).
Throughout the world myopia is a common cause for visual disability particularly in underdeveloped countries where the health care is poor or even non-existent. Myopia currently affects over 1.5 billion worldwide and thisis expected to increase to approximately 2.5 billion by the year 2020 (Dirani et al., 2006a). Prevalence varies between countries and ethnicities, reaching as high as 9 out of 10 people affected in some Asian populations such as Singapore and China (Chow et al., 1990; Wong et al., 2000). Epidemiological studies show that the prevalence of myopia is increasing and this is becoming a significant public health problem (Fredrick, 2002; Paluru et al., 2003; Saw et al., 1996). As well as needing resources for optical correction of myopia, the associated increased risk of vision loss has further economic and social implications for the population. Therefore extensive research is being carried out to understand the mechanisms and factors underlying myopia development in aid to prevent the incidence of myopia.
An emmetropic eye is one that has zero or negligible refractive error. Most babies are born hypermetropic (long-sighted) and emmetropisation is the process by which the eye goes through changes to reach emmetropia, this occurs within the first 5-8 years of life (Fredrick, 2002). The simple reason for the increasing prevalence of myopia may be due to changes in environment, especially modernisation of the underdeveloped world which is partly due improved education infrastructure and the technological/internet revolution. This means people are now using their eyes for near tasks such as computing much more than before. Therefore this near visual experience may have some influence in the emmetropisation process, resulting in the eyes becoming myopic instead of emmetropic. However there are many studies, such as twin and family history studies that have also found a strong positive correlation between genetics and myopia (Hammond et al., 2001). Other studies have mapped particular genes that influence the onset of myopia or predispose an individual to becoming myopic. It seems there is some interaction between environment and genetics and how they influence the onset and progression of myopia but the relative contribution of each is not fully understood (Saw et al., 1996).
Identifying potential myopia disease genes will help understand the pathophysiological mechanisms behind myopia development. The potential for this in the future would be the ability to identify individuals at risk from myopia and help develop preventative therapies TANG2008. This dissertation will aim explore the role of genetics in myopia and review the current genes that have been identified to be associated with myopia.
There are multiple ways to help identify genes associated with myopia, and researchers often employ a combination of techniques to further validate their findings. Genes are identified using genetic markers and genetic mapping techniques, these are explained further below.
A genetic marker is a gene or DNA sequence with a known location on a chromosome. It is usually described as a variation, which may be due to mutation or alteration in the genomic loci. This variation is what helps researchers identify genes associated with a particular trait like myopia. Genetic markers can be short DNA sequences, such as single nucleotide polymorphism (SNP), or long sequences such as microsatellites.
SNPs are polymorphic markers that are variations in the DNA sequence occuring when a single nucleotide in the genome differs between two members of the same species (Warthmann et al., 2007). For example people with myopia will have a common SNP compared to those without.
TANG2008Microsatellites are short sections of DNA made up of repeating units containing 10-60 base pairs. Although microsatellites may have different or unknown repeating units, the repeating unit within the microsatellite is relatively constant (Dorland, 2007). The number of repeating units varies between individuals in a species. Microsatellites have a high level of polymorphism that makes them another useful tool to help identify genetic markers.
Genetic mapping - linkage analysis
The aim of genetic mapping is to assign DNA fragments to chromosomes, which eventually accumulates to a complete genetic map for a condition. Linkage analysis is based on the link between loci (locations of genes). If two loci are inherited together on the same chromosome then they are said to be linked. Meiosis results in genes being recombined from parent chromosomes into a new combination and this crossing over of DNA can cause alleles previously on the same chromosome to be separated. Therefore if two loci are closer together then the possibility of them being inherited together is greater i.e. there is a reduced chance of alleles TANG2008being separated and therefore the offspring is more likely to inherit parental traits. Linkage studies aim to uncover genetic markers that are linked to disease genes with the potential to identify other genes as possible disease gene candidates (Terri et al., 2004).
Genetic mapping - genetic markers, linkage & association studies.
Complex trait genetics - myopia susceptibility gene loci etc.
GENETIC INFLUENCE ON MYOPIA
Twin studies - much more correlation in DZ twins than MZ twins.
Familial studies - heredity influence.
Environmental factors - precursor for genetic influence?
Other genes etc.
Credibility of mapping techniques.
Genes & environment relationship.
How all of above may contribute to onset/progression of myopia.