Molecular genetic aspects of complicated myopia pathogenesis

Abstract

Complicated myopia (CM) is not only a refractive error but a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and the axial length that causes the image to be focused off the retina. Genetic factors in progressive myopia play a key role in determining the impact of ecologic factors on refraction development. The majority of genetic variants underlying CM are characterized by modest effect and/or low frequency, which makes them difficult to identify using classic genetic approaches. The genes identified to date account for less than 10% of all myopia cases, suggesting the existence of a large number of yet unidentified low-frequency and/or small-effect variants, which underlie the majority of myopia cases. Genome analysis revealed dozens of loci associated with non-syndromic myopia, and showed that refractive errors are associated with mutations in genes that are involved in the growth and development of the eye by regulating ion transport, neurotransmission, remodeling of extracellular matrix of the retina and other ocular structures. Genetic study of refractive error provides a unique opportunity to detect key molecules that may play important roles in the development of refractive error. Identifying the molecular basis of refractive error helps to understand mechanisms, and subsequently to design rational therapeutic intervention for this condition.