The Genetics of Myopia - Term Paper Example

Genetics of Myopia Introduction Myopia, also known as near sightedness, is one of the refractory errors of the eye in which the image that is focused falls anterior to the eyes retinal photoreceptor layer (Young, 423). It is infact the most common eye disorder in humans. When present in a severe form, it can contribute to several blinding disorders like macular degenration, glaucoma, premature cataracts and retinal detachment (Young, 423). Hence it is a major public health concern. The eye length in myopia is long and any etiology must account for the elongation of the axis. Until now, no single theory has been developed to ascertain the cause of myopia. While erstwhile researchers have attributed this to hereditary, the increased incidence of this disease with increasing age was considered to be a "statistical curiosity" (Mutti). Currently both environmental and genetic mechanisms have been incriminated in the etiology of the disease. Researchers are interested in identifying genetic loci of myopial disease because understanding of the genetics of the most common refractory error provides insight into the molecular basis of the disease and also helps in the identification of the pathways of growth and development of the eye, thus providing scope for research and development of effective therapies that prevent the development of the disease (Hornbeak and Young, 356). In this research article, genetics of myopia will be discussed through review of appropriate literature. Role of genetics in myopia The pathogenesis of myopia is not well understood, but there is enough evidence to incriminate genetic factors in the development of the disease, especially the severe form, in which the spherical refractive power is 5 diopters or more. Studies have identified multiple genetic loci for high-grade and moderate-grade myopia, but, as of now, susceptibility genes of myopia are still unknown (Young, E8). According to the genetic theory, defective genes cause elongation of the eye from front to back due to faults in the process of development, causing focussing of images in the front of the retina and not directly on it as in normal individuals. Genetic factors can also weaken or cause degradation of the connective tissue by acting by several biochemical means, thus causing abnormal length of the eyeball. Some researchers opine that environmental factor exaggerate the development of condition which is already predisposed by genetic abnormality. Several studies have reported positive correlation between myopia in parents and myopia in their children, pointing to the hereditary nature of myopia. Infact, epidemiological studies have shown that children born to myopic parents have less chances of developing hypermetropia, have anterior chambers that are deeper than children with no family history of myopia and possess longer vitreous chambers much before the onset of myopia. These aspects strongly imply the role of genetics in the development of myopia. Experts opine that it is difficult to ascertain the impact of genetics on the development of myopia through epidemiological studies because; children are likely to adopt parental behaviours like near-work activities which contribute to myopia and this, is a major confounding factor (Young, 423). According to Drexler, increased reading causes contraction of the ciliary muscle and thus causes elongation of the eye ball. In children, near work and night light exposure have been attributed to be important environmental factors for the development of myopia (Young, 429). In individuals with moderate myopia, environmental factors also have been identified in the pathogenesis, along with genetic factors, based on several animal studies. Evidence for this comes from the fact that children with media irregularities and educational achievements have higher chances of development of myopia. Even juvenile-onset myopia has been attributed to genetic-environmental interaction, and genes for this type of myopia are have not been identified so far. The reason for this is that in this type of myopia, the genes are of small effect or intermediate effect and to detect these genes using independent pedigrees is very difficult. Another aspect which strongly links high myopia with genetic involvement is the fact that several genetic syndromes like Stickler syndome and Marfan syndrome have myopia as a consistent clinical finding (Young, 424). Myopia has high prevalence and has a wide clinical spectrum. It also has genetic heterogeneity. Because of these factors, it has been difficult to ascertain the role of clinical factors. Main contributors to suspicion of genetic involvement are twin studies and familial aggregation (Goss, 875). Several twin studies have identified myopic refractive error components in monozygotic twins when compared with dizygotic twins. In twin studies, defective versions of the gene PAX6 have been identified (Goss, 875). The exact mode of inheritance is yet unclear. Many studies in the past have proposed different modes of inheritance. Of particular interest is the study by Goss et al (875) who conducted a systematic review and opined that the most common mode of inheritance is the autosomal dominant one. The review also suggested autosomal recessive and X-linked inheritance in a few pedigree studies. So far, a minimum of 18 loci in 15 different chromosome have been identified as linked with myopia. Many of them are yet to be confirmed although. Several studies have identified specific candidate genes, which are not a part of the identified myopia or MYP loci (Jacobi and Pusch, 359). Most experts agree that genetic mechanism of myopia is a complex phenomenon with several genes acting in concert to cause the disease (Jacobi and Pusch, 359). In a recent study by Guo et al (p.1473), the researchers investigated a Chinese family with severe nonsyndromic myopia. The mode of inheritance was X-linked recessive. Linkage analysis in this family was mapped to Xq28, a 6.1-cM region between DXS8069 and Xqter (MYP1 region). previous researchers also identified this locus with reference to X-linked recessive inheritance. This locus has been designated as myopia locus-1 or MYP-1 and myopia associated with it is known as Bornholm eye disease, named after the family which was studied for genetic mapping (Young, 423). In another recent study by Ma et al (2043), on a Chinese family, in which the mode of inheritance was autosomal dominant, the genetic locus was identified as chromosome 5p13.3-p15.1. Other loci of autosomal dominant inheritance which have been identified are 18p11.31(MYP2), 12q23.1-24 (MYP3), 17q21- 22 and 7q36 (/MYP4). In the MP2 region also, several candidate genes have been identified. Health et al (2001) studied high myopia with autosomal dominant inheritance in an Italian patient population and identified independent confirmations of MYp2 locus. Another similar study on Hong Kong Chinese descent patient population also identified a independent MP2 focus (Lam, 115). Zhang et al (p.554) studied a Chinese family and autosomal dominant inheritance was mapped to 4q22-q27. Studies which have evaluated families with autosomal recessive inheritance have identified one locus at 14q22.1-q24.2 in a 25.23 Mb region between markers D14S984 and D14S999. Some researchers have attributed the pathogenesis of myopia to changes in sclera and genetic abnormalities of sclera can in turn contribute to development of myopia, thus indirectly influencing the development of myopia. genetic abnormalities which affect collagen have been incriminated in several collagen related syndromes, of which myopia is also a part. This is known as the candidate gene hypothesis. The hypothesis is that "the nonsyndromic high myopias result from distinct, but analogous, developmental defects of scleral wall growth control, and that their causative genes may be functionally or structurally related to one another and have parallel functions in the development of the visual axis" (Young, p.426). MYP2 is one of the genes that has been linked to protein defect of sclera, in this regard. Conclusion The exact pathogenesis and etiological factors of the most common disease of the eye, myopia is yet unknown. In the severest form of the disease, there is strong correlation to genetic susceptibility based on occurrence in several genetic syndromes, high familial aggregation and several twin studies. So far, loci have been identified on 15 chromosomes, but their exact role in the pathogenesis of the disease remain unclear. Complex interaction between environmental factors and genetic susceptibility have been considered in mild and moderate forms of myopia. 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