Genomic strategies to understand causes of keratoconus (original) (raw)

Molecular Genetics and Genomics

com thinning, which results in the conical shape of the cornea. These structural changes in the corneal layers induce optical aberrations, leading to a loss of visual acuity due to distorted blurred vision, which is caused by irregular astigmatism, and high myopia (Rabinowitz 1998). Although KTCN is sometimes referred to as a corneal dystrophy, it is not included in International Classification of Corneal Dystrophies (IC3D) (Weiss et al. 2008) and should be distinguished from this group of corneal diseases. However, co-occurrence of KTCN with many types of corneal dystrophies, including Avellino and Fuchs dystrophies (Igarashi et al. 2003; Salouti et al. 2010; Wilson et al. 2014), may indicate that common molecular mechanisms in the pathogenesis of these disorders are involved. Among the general population, the estimated frequency of KTCN is 1 in 2,000 individuals (Rabinowitz 1998), although up-to-date data are not available. The prevalence of KTCN may be different according to patient ethnic origin (Gokhale 2013). The reported prevalence of the disease may also vary depending upon the different diagnostic tests used in the particular studies. The early KTCN or forme fruste KTCN are not detectable at the slit lamp during the anterior segment examination, and in these cases, assessment of the corneal topographic pattern is required to obtain the accurate diagnosis (Saad and Gatinel 2010). The first symptoms of KTCN usually appear during the second decade or early in the third decade of life. The pathogenic features of KTCN may be observed in different layers of the cornea (Fig. 1) (Sherwin and Brookes 2004). These abnormalities include changes in morphology of epithelial cells (Sykakis et al. 2012), deposition of iron particles in the epithelial basement membrane, breaks in Bowman's layer (Rabinowitz 1998), and thinning of stroma correlating with loss of collagen lamellae, altered collagen fibril orientation, and decreased keratocytes density (Patey et al.