On the 14th of September 2010 a report was published in the BBC News Magazine by Tom Geoghegan1, in which the content guarantees to change the standard of living of many people. With the eye catching headline “Could glasses soon be history?” it attracts the attention of many readers, especially of those who wear spectacles. It tells about new research by scientists, who discovered a gene which has the potential to cause short-sightedness, however the report describes the scientific background regarding this discovery in a more superficial manner. It holds its main focus of attention on the way in which glasses are integrated in our society nowadays. It mentions briefly why in times gone by it was very unlikely for people to wear glasses, how people were teased by needing glasses. Nowadays they are more accepted and have become a kind of accessory. So even if someone does not need to wear glasses, they do it anyway. In taking this focus the articles attention is off the point, it overshadows the science behind the topic “short - sightedness and its genetic cause”.
Short – sightedness or myopia, measured by spherical equivalent in dioptres, is the most common form of eye disorders or ametropia. It is one of the three commonest refractive errors, whereby the affected person is not able to see distant objects properly. To be able to see images defined, the focal point of the light rays has to be on the retina. Otherwise you see just blurred images. In myopia the parallel rays of light do not focus on the retina to give a sharp pattern; their focus point is rather more in front of the retina, whereby the blurred visual impression is evoked. The development of the impairment is associated with structural changes of the eye which causes the myopia. Myopic eyes also have an elongated eye axis, their vitreous chambers are larger, the anterior chambers are deeper and the lenses are thinner than in non – myopic eyes.
Besides myopia there exist three more common refractive errors: far – sightedness or hyperobia, where you see the closer objects blurred due to a shortened eye axis; and astigmatism, where you see the images out of focus because of the cornea, which is curved in an irregular way. A fourth condition, which could be seen as a sort of short – sightedness, is presbyopia. This condition mostly occurs in later years due mainly to the loss of elasticity of the crystalline lenses.
However the common short – sightedness (myopia) starts usually in childhood. In the last few years the amount of people affected by myopia has increased steadily. The WHO (World Health Organization) estimates that worldwide more than 153 million people are living with visual detraction and this number does not comprise of the older people affected by presbyopia2. But this approximation is difficult to calculate. The estimated number of unreported cases is presumably much higher, because mainly of the difficulty in the third world to count the affected individuals. Numerous people do not have the possibility to test their eyes due to the poor infrastructure.
According to a study in Western Europe)3 myopia alone (more severe then - 1 diopter) affects 26,6 % of the adults in Western Europe (relates to people 40 years and older). In this study the US has a similarly affected adult cohort, with around 25 %. But according to the adults affected of 20 years and older the number increases to even 33 % for the US4. But this is a small number compared to East Asia, where 80 % of the young adults are affected5. Furthermore a clinically critical myopia is the commonest cause of blindness in working age populations in some countries. So it would be very interesting to discover the causes of myopia and try to develop a medicine. But currently no practical therapies exist to prevent the developing of myopia or even to heal it.
As aforementioned the causes or the mechanism for myopia are still not fully understood. The aetiology is very complex and to this date largely uncharacterized. It is given if your family is affected, especially when your parents are short – sighted, that you often become short – sighted too. Also the environment plays a clear role in the development of myopia. Several risk factors like education, reading in the twilight, urbanization, looking for a long time at TV or computer screens, outdoor exposure and close up work with the potential to strain the eyes could increase myopia.
But in recent research it was discovered that there is also a huge genetic aspect which leads to myopia. Numerous studies suggest that genetic heritability might be as high as 80%6. The BBC – report names mainly one gene as the cause for myopia, probably to keep it simple. But verisimilar the genetic basis does not result from only one individual gene. Several segregation analyses suggested multiple genes, several candidate loci, rather than a single key gene. Nonetheless the BBC report refers to one of these studies, where they found a gene sector which presumably could cause myopia. They also refer to another study, where they found a different DNA – region likely causing myopia. So they presume that several genes, several gene – regions, could be the possible initiators of myopia. Therefore it is assumed that the complexity of myopia is induced by multiple genetic and environmental effects, which lead to individual variation in myopia.
The research of Hysi et al.7, to which the report refers, conducted a genome – wide association study (GWAS) for refractive errors. The study was based in the British TwinsUK adult registry cohort with circa 4000 individuals. This analysis was replicated in six European cohorts, in which there were a total circa 13500 individuals. They discovered a genome – wide significant region, 120 kb sized, on chromosome 15q25, in which they found multiple single nucleotide polymorphisms (SNPs) which could have been associated with refractive errors. All the identified SNPs were in high linkage disequilibrium with one another. That means that the frequencies of their association occurred in this analysis was not random. The loci of the SNPs in this area overlap with the transcription initiation site of a gene called RASGRF1. This gene is found to be highly expressed in neurons and what is more interesting, in the retina. RASGFR1 stands for Ras protein – specific guanine nucleotide – releasing factor 1, which is a large gene, spanning about 130 kb with 28 unknown exons and multiple alternative mRNA transcripts. It is involved in several processes, like learning, visual processing and muscarine signalling pathways 7, which is likely to be associated with myopia. In addition the scientists made a computer simulation, wherein they could show possible gains or losses in the transcription factor – binding site of the RASGRF1 – gene due to the SNPs in the 15q25 – region. The protein expressed by this gene activates RAS, which can be found in high quantities in human retinas, with the highest concentrations in the early developmental phases of the eye. The concentration of RAS fades with time, but is still present in the retina. So it could be said, that RASGRF1 impacts the development of the eye. For more affirmation for this theory the investigators demonstrated that a lack of RASGRF1 – expression in knockdown mice (RASGRF11/1) produces namely a normal retina, but it also causes deficits in photoreception and visual sensory processes and changes furthermore the downstream expression of many genes. It seems that RASGRF1 is integrated in the upkeep of the normal function of the retina and probably in the signalling pathways affecting myopia.