原发性开角型青光眼相关基因及发病机制研究进展

青光眼是一种视神经病变，是全球不可逆性失明的主要原因，其发病机制目前尚不完全清楚。近年 来，随着全基因组关联研究（GWAS）、家系研究和功能学研究的深入，人们对青光眼的分子基础和 复杂性的认识也有了较大的进展。原发性开角型青光眼（POAG）占全世界青光眼病例的70%左右， 且患病率一直在增加。POAG具有明显的遗传特征，但因其遗传方式复杂，仅有约10%的病例表现 为典型的孟德尔单基因遗传模式，其他的则可能是多个遗传因素的相互影响，或者是遗传因素和环 境因素共同作用的结果。目前已明确与青光眼直接相关基因达30余个，其编码蛋白参与了广泛的细 胞进程和生物系统，包括细胞外基质、细胞因子信号转导、脂质代谢、膜生物学、细胞分化、自噬和 眼发育的调节等生物学进程。本综述拟从内质网应激反应、肿瘤坏死因子-α信号通路与自噬调节、 TGF-β信号通路等几个重要的生物学角度来深入认识青光眼与基因之间的内在关联，进一步明确其 可能的发病机制。

Advances in Genetics and Pathogenesis in Primary Open Angle Glaucoma

Glaucoma is a type of optic neuropathy. It is the main cause of irreversible blindness in the world. Its pathogenesis is unclear at this time. In recent years, with the development of a genome-wide association study (GWAS), family studies and functional studies, great progress has been made in the understanding of the molecular basis and complexity of glaucoma. Primary open angle glaucoma (POAG) accounts for about 70% of glaucomatous cases worldwide and the prevalence rate has been increasing. POAG has obvious genetic characteristics, but since it is a complex genetic pattern, only about 10% of the cases represent a typical Mendelian single gene inheritance, and the others may be the interaction of multiple genetic factors, or the result of the common effects of genetic and environmental factors. At present, more than 30 genes directly related to glaucoma have been identified. The encoding proteins are involved in a wide range of cell processes and biological systems, including the extracellular matrix, cytokine signal transduction, lipid metabolism membrane biology, cell differentiation, autophagy and eye development. This report intends tofurther the understanding of the internal relationship between glaucoma and genes and clarify its possible pathogenesis from several important biological processes such as endoplasmic reticulum stress response, tumor necrosis factor-alpha signal pathway, autophagy regulation, TGF-beta signal pathway and others.