Monday September 13 2010
Sight problems can have numerous causes
Short-sightedness could soon be remedied with eye drops rather than glasses, The Daily Telegraph reported. Several other newspapers also predicted that glasses will become obsolete after research linked genetic variations to the common eye problem.
The news is based on two well-conducted genetic studies that together tested the DNA of over 25,000 people from across Europe. It found that short-sighted people were more likely to possess up to three particular genetic variants, which the researchers say make a small contribution to the chances of having the condition.
The researchers note that their findings highlight that the genetic component of short-sightedness is likely to be determined by several additional genetic variants acting together. Given this interpretation, the optimism shown in the newspapers is surprising. One lead researcher reportedly said that developing a treatment from these findings would be “a challenge” and will take at least 10 years. However, this cautious and realistic interpretation was not reflected in all news reports.
Where did the story come from?
The news is based on a pair of related studies that were carried out by researchers from King’s College in London and research centres throughout the world, including Spain, Australia and China. The studies were funded by a variety of organisations including the Wellcome Trust, the EU and the US National Institutes of Health. Both research papers were published online in the peer-reviewed medical journal Nature Genetics.
The story was picked up by several newspapers, all heralding in some way or another an end to short-sightedness. This optimism is premature. The presence of the genetic variants may make people more susceptible to short-sightedness, but not all short-sighted people possess the gene variants and not everyone with the variants is short-sighted. Environmental factors such as education, urban living, outdoor activity and carrying out close-up work may also play a role, as may further variants still waiting to be discovered. The researchers’ interpretation of their results is more cautious than those featured in newspapers.
What kind of research was this?
The studies were two separately published but similar genome-wide association studies. This type of study involves the analysis of genetic sequences of individuals with and without a particular condition, in this case myopia, commonly known as short-sightedness. This allows researchers to compare their DNA and identify genetic variations that are more common in people with the condition.
Normally, the eye focuses the viewed image onto the retina, the light-sensitive area at the back of the eye. In myopia, there is a “refractive error” where the image is focussed in front of the retina instead of onto it. This causes distant objects to appear blurred, while those nearer to the eye are clearer. These problems can lead to changes in the structure of the eye and further complications such as glaucoma and retinal detachment.
Factors that are linked to the development of myopia include education, reading and outdoor activity, but there is also a genetic component to the condition as it tends to run in families. In these two studies, the researchers attempted to identify the genetic variants that might be associated with the condition.
What did the research involve?
In the first study, the initial sample comprised 5,328 people from Holland. This included 2,790 people with a mixture of refractive disorders, either long-sightedness (hyperopia) or short-sightedness (myopia). The remainder did not have these eye problems. The DNA sequences of all participants were scanned and the occurrence of variants compared between those with eye problems and those without.
In a second step, the researchers attempted to replicate their findings from the first sample in four separate, independent samples (with a combined total of 10,280 people). This is a common approach to validating findings in these types of genetic-profiling studies.
The second study started with a sample of 4,270 people from the UK. This sample was also used as a replication sample in the above study. The participants’ DNA was examined and any variants more common in those with a refractive disorder were identified. The researchers replicated their findings in six separate European samples, featuring a total of 13,414 individuals. In this study, the researchers also examined the DNA of mice, investigating the functioning of a gene that was located near to a gene variant identified in humans.
What were the basic results?
The first study identified a gene variant called rs634990 on chromosome 15q14 that was most strongly associated with short-sightedness. Short-sightedness was 1.83 times more likely than long-sightedness if a person was carrying two copies of the variant. This particular variant is situated near genes that are involved in certain processes in the eye.
The second study found that two other variants, rs939658 and rs8027411 on chromosome 15q25, were most strongly associated with short-sightedness. People with two copies of the variant rs8027411 were 1.16 times more likely to have myopia than no eye problems. In mice, the variant was near a gene associated with the maintenance of normal functioning of the retina.
How did the researchers interpret the results?
The researchers have identified common genetic variants that influence people’s susceptibility to myopia. The identification of these variants is important to understand “the molecular mechanism responsible for the most common cause of visual impairment”.
The studies have identified genetic variants in regions of the DNA that are linked to eyeball function. They do not yet explain how problems in these genes could lead to short-sightedness or indeed why only some people with these variants are short-sighted.
The fact that a gene variant increases the susceptibility to a condition does not mean that it causes it. As the researchers note, the condition is likely to be caused by many different gene variants. It is not yet known if these are the most important variants or indeed how they may interact with the environmental factors associated with myopia or any undiscovered variants in nearby genes.
It is too soon to know how these findings can translate into treatments for people with myopia. If they do, as with most treatments for eye conditions, they may take the form of a tablet or eye drops. However, according to one of the lead researchers, "it is going to be a challenge and at least 10 years before there is a treatment."
Most importantly, the contribution of these gene variants to the risk of myopia is described as “small”. The researchers say this shows that refractive errors are caused by a number of different genetic variants in addition to the initial few found in these studies.