Role of Endostatin Gene Polymorphism in the Development of High Myopia

Myopia is a common ocular disorder characterized by refractive error affecting 30% of general population. High myopia (>6D) is caused by excessive axial elongation that primarily involves the ora-equatorial area and the posterior pole. Pathological myopia often accompanied by glaucoma, cataracts, macular degeneration, and retinal detachment, gradually leading to vision loss. Recent population and family based studies provided evidence for a genetic-component to pathologic myopia. Study on potential candidate genes for myopia through the genomic study of pathological myopia can help in identification of myopia genes. During myopia, retinal defocus effects mechanosensitivity of the eye causing excessive axial elongation, which is associated with altered scleral collagen architecture and defective mechanotransduction. Ocular signal transduction from retina-RPE complexes is mainly effected during scleral remodeling. The most important effectors in scleral coats are collagens, proteoglycans, Matrix metalloproteinases (MMP’s) and tissue inhibitors of matrix proteinases (TiMP’s). The difference of SNPs in different genes might contribute the formation of scleral thinning during myopia development. The endostatin (20 KDa C-terminal fragment of collagen XVIII) has an essential role in ocular development and the maintenance of visual function. In Age-dependent loss of vision the endostatin mutant is associated with pathological accumulation of deposits under the retinal pigment epithelium. Endostatin RNA also blocks the axis duplication induced by beta catenin, partially inhibits Wnt-dependent transcription, and stimulates degradation of beta catenin during the lens development of eye. Hence, the present study on high myopia (n=152) has been planned to analyze collagen XVIII/endostatin gene polymorphism (D104N) and to understand its functional significance in ocular growth. The association of endostatin gene was analyzed through PCR-RFLP method which resulted in 3 genotypes (DD, DN, and NN). The comparison of gene and genotype frequencies calculated revealed increase in DN genotype frequency in females, non-familial cases, in cases with age at onset group >20yrs and refractive error above >10D. The results indicate that there is risk for myopia progression in individuals with this genotype. Further studies on endostatin can throw light on better understanding of its role in ocular development and help in management of myopia.