The vast complexity of primary open angle glaucoma: Disease genes, risks, molecular mechanisms and pathobiology
The vast complexity of primary open angle glaucoma: Disease genes, risks, molecular mechanisms and pathobiology
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DOI：
10.1016/j.preteyeres.2013.09.001
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发表时间：
2013-11-01
影响因子：
17.8
通讯作者：
Bergen, Arthur A. B.
中科院分区：
文献类型：
--
作者：
Janssen, Sarah F.;Gorgels, Theo G. M. F.;Bergen, Arthur A. B.
原发性开角型青光眼（Primary open angle glaucoma，POAG）是一种复杂的进行性视神经病变，由环境和遗传因素共同触发。几种眼组织，包括睫状体、小梁网和视神经乳头，甚至可能是脑组织，都参与了导致POAG的一系列病理事件。POAG的遗传风险证据来自涉及少量疾病基因的家族联系研究（MYOC，OPEN，WDR 36）。最近的全基因组关联研究（GWAS）鉴定了大量新的POAG基因座和疾病基因，如CAV 1、CDKN 2B和GAS 7。在本研究中，我们回顾了120多个家庭和GWA研究。我们总共选择了65个（候选）POAG疾病基因，并继续评估其功能，POAG相关眼组织中的mRNA表达和疾病状态的可能变化。我们发现，对应于这65个（候选）POAG疾病基因的蛋白质参与了少至四个共同的功能分子网络。归因于这4个网络的功能是发育（dys）功能，脂质代谢和炎症过程。对于65个POAG疾病基因，我们回顾了现有的POAG（转基因）小鼠模型，这可能是有用的，为未来的功能研究。最后，我们发现，65个（候选）POAG基因大大增加了特异性和敏感性的判别POAG风险测试。这表明POAG的个人风险评估和个性化药物即将出现。总之，所提供的数据对于理解遗传变异在POAG中的作用是必不可少的，并可能为理解POAG以及其他神经退行性疾病（如阿尔茨海默病）的病理生理学提供线索。(C)2013爱思唯尔有限公司保留所有权利。
Primary open angle glaucoma (POAG) is a complex progressive optic nerve neuropathy triggered by both environmental and genetic risk factors. Several ocular tissues, including the ciliary body, trabecular meshwork and optic nerve head, and perhaps even brain tissues, are involved in a chain of pathological events leading to POAG.Genetic risk evidence for POAG came from family linkage-studies implicating a small number of disease genes (MYOC, OPEN, WDR36). Recent Genome Wide Association Studies (GWAS) identified a large number of new POAG loci and disease genes, such as CAV1, CDKN2B and GAS7. In the current study, we reviewed over 120 family and GWA studies. We selected in total 65 (candidate) POAG disease genes and proceeded to assess their function, mRNA expression in POAG relevant eye tissues and possible changes in disease state. We found that the proteins corresponding to these 65 (candidate) POAG disease genes take part in as few as four common functional molecular networks. Functions attributed to these 4 networks were developmental (dys)function, lipid metabolism, and inflammatory processes. For the 65 POAG disease genes, we reviewed the available (transgenic) mouse models of POAG, which may be useful for future functional studies. Finally, we showed that the 65 (candidate) POAG genes substantially increased the specificity and sensitivity of a discriminative POAG risk test. This suggests that personal risk assessment and personalized medicine for POAG are on the horizon. Taken together, the data presented are essential to comprehend the role of genetic variation in POAG, and may provide leads to understand the pathophysiology of POAG as well as other neurodegenerative disorders, such as Alzheimer's disease. (C) 2013 Elsevier Ltd. All rights reserved.