Bringing the age-related macular degeneration high-risk allele age-related maculopathy susceptibility 2 into focus with stem cell technology.
Bringing the age-related macular degeneration high-risk allele age-related maculopathy susceptibility 2 into focus with stem cell technology.
复制标题
利用干细胞技术使年龄相关性黄斑变性高危等位基因年龄相关性黄斑病易感性2成为焦点
DOI：
10.1186/s13287-017-0584-4
复制
发表时间：
2017-06-06
影响因子：
7.5
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Sun S;Li Z;Glencer P;Cai B;Zhang X;Yang J;Li X
年龄相关性黄斑变性（AMD）是发达国家老年人失明的主要原因。它是一种由环境和遗传因素共同引发的多因素疾病。高温要求A丝氨酸肽酶1 （HTRA1）和年龄相关性黄斑病变易感性2 （ARMS2）是与AMD密切相关的两个基因。由于ARMS2是一个进化较晚的灵长类特异性基因，而且ARMS2/HTRA1基因位于染色体10q26上一个连锁不平衡较强的区域，因此很难区分单个基因的功能。因此，有必要关注这些基因。患者特异性诱导多能干细胞（iPSC）衍生的视网膜色素上皮（RPE）提供了对患者遗传学的直接访问，并允许识别RPE相关退行性疾病的启动事件的可能性。本文就近年来AMD的流行病学研究进展作一综述。提出了ARMS2基因与AMD之间存在明确相关性的论点。综述了ARMS2基因分型在医学治疗中的应用。介绍了几种基于iPSCs等干细胞的arms2相关遗传模型。本文还讨论了应用基因编辑技术和干细胞技术更好地探索ARMS2高危等位基因机制的可能性，这将为治疗提供重要指导。
Age-related macular degeneration (AMD) is a major cause of blindness in older adults in developed countries. It is a multifactorial disease triggered by both environmental and genetic factors. High-temperature requirement A serine peptidase 1 (HTRA1) and age-related maculopathy susceptibility 2 (ARMS2) are two genes that are strongly associated with AMD. Because ARMS2 is an evolutionarily recent primate-specific gene and because the ARMS2/HTRA1 genes are positioned at a locus on chromosome 10q26 in a region with strong linkage disequilibrium, it is difficult to distinguish the functions of the individual genes. Therefore, it is necessary to bring these genes into focus. Patient-specific induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) provides direct access to a patient’s genetics and allows for the possibility of identifying the initiating events of RPE-associated degenerative diseases. In this paper, a review of recent epidemiological studies of AMD is offered. An argument for a definite correlation between the ARMS2 gene and AMD is presented. A summary of the use of ARMS2 genotyping for medical treatment is provided. Several ARMS2-related genetic models based on such stem cells as iPSCs are introduced. The possibility of applying gene-editing techniques and stem-cell techniques to better explore the mechanisms of the ARMS2 high-risk allele, which will lead to important guidance for treatment, is also discussed.