Desmettre T
Centre de rétine médicale, 187, rue de Menin, 59520 Marquette-Lez-Lille, France; London International Medical Centre, 18-22 Queen Anne Street, London, W1G 8HU, Royaume-Uni.
J Fr Ophtalmol. 2018 Dec;41(10):981-990. doi: 10.1016/j.jfo.2018.06.004. Epub 2018 Nov 16.
Age-related macular degeneration (AMD) is a complex multifactorial condition involving multiple genetic, environmental and constitutional factors. Inflammation, oxidative stress and lipid metabolism seem to be the most important factors in the pathogenesis of the disease. The importance of genetic factors has mainly been revealed with the influence of histocompatibility complement factor H (CFH) variations and the ARSM2 susceptibility gene. Another component, epigenetics, could help to explain some of the relationships between environmental and genetic factors. Epigenetics is defined as the study of modulations of gene activity that can be transmitted over cell divisions without involving mutation of the DNA sequence. The molecules that are involved in these mechanisms are referred to as the epigenome. The mechanisms involve DNA methylation, histone modification, chromatin remodeling, and gene inhibition by non-coding RNA. Epigenetics could explain how the environment may induce relatively stable changes in traits or even diseases, possibly inheritable over several generations. Epigenetic traits established during development, and/or acquired under the influence of nutritional factors or other environmental factors, could influence the interactions between genes and the environment. Several authors have recently shown the influence of epigenetic factors in the pathogenesis of ocular diseases such as cataract, dry eye, glaucoma, diabetic retinopathy and more recently AMD. A better understanding of the involvement of genetic variants at risk, their relationship with epigenetics and environmental factors would certainly help to better assess the risk of developing AMD or better understand recent changes in the incidence of the disease.
年龄相关性黄斑变性（AMD）是一种复杂的多因素疾病，涉及多种遗传、环境和体质因素。炎症、氧化应激和脂质代谢似乎是该疾病发病机制中最重要的因素。遗传因素的重要性主要通过组织相容性补体因子H（CFH）变异和ARSM2易感基因的影响得以揭示。另一个因素，表观遗传学，有助于解释环境因素与遗传因素之间的一些关系。表观遗传学被定义为对基因活性调节的研究，这种调节可在细胞分裂过程中传递而不涉及DNA序列的突变。参与这些机制的分子被称为表观基因组。这些机制包括DNA甲基化、组蛋白修饰、染色质重塑以及非编码RNA介导的基因抑制。表观遗传学可以解释环境如何在性状甚至疾病中诱导相对稳定的变化，这些变化可能在几代人中遗传。在发育过程中建立的和/或在营养因素或其他环境因素影响下获得的表观遗传性状，可能会影响基因与环境之间的相互作用。最近有几位作者表明表观遗传因素在白内障、干眼症、青光眼、糖尿病视网膜病变以及最近的AMD等眼部疾病的发病机制中发挥作用。更好地理解风险遗传变异的参与情况、它们与表观遗传学和环境因素的关系，肯定有助于更好地评估患AMD的风险，或更好地理解该疾病发病率最近的变化。
