Exploring the contribution of ARMS2 and HTRA1 genetic risk factors in age-related macular degeneration

IF 18.6 1区医学 Q1 OPHTHALMOLOGY Progress in Retinal and Eye Research Pub Date : 2023-11-01 DOI:10.1016/j.preteyeres.2022.101159

Yang Pan , Yingbin Fu , Paul N. Baird , Robyn H. Guymer , Taraprasad Das , Takeshi Iwata

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引用次数: 4

Abstract

Age-related macular degeneration (AMD) is the leading cause of severe irreversible central vision loss in individuals over 65 years old. Genome-wide association studies (GWASs) have shown that the region at chromosome 10q26, where the age-related maculopathy susceptibility (ARMS2/LOC387715) and HtrA serine peptidase 1 (HTRA1) genes are located, represents one of the strongest associated loci for AMD. However, the underlying biological mechanism of this genetic association has remained elusive. In this article, we extensively review the literature by us and others regarding the ARMS2/HTRA1 risk alleles and their functional significance. We also review the literature regarding the presumed function of the ARMS2 protein and the molecular processes of the HTRA1 protein in AMD pathogenesis in vitro and in vivo, including those of transgenic mice overexpressing HtrA1/HTRA1 which developed Bruch's membrane (BM) damage, choroidal neovascularization (CNV), and polypoidal choroidal vasculopathy (PCV), similar to human AMD patients. The elucidation of the molecular mechanisms of the ARMS2 and HTRA1 susceptibility loci has begun to untangle the complex biological pathways underlying AMD pathophysiology, pointing to new testable paradigms for treatment.

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探讨ARMS2和HTRA1基因在老年性黄斑变性中的作用。

年龄相关性黄斑变性（AMD）是65岁以上人群严重不可逆中心视力丧失的主要原因。全基因组关联研究（GWASs）表明，年龄相关性黄斑病变易感性（ARMS2/LOC387715）和HtrA丝氨酸肽酶1（HTRA1）基因所在的染色体10q26区域是AMD最强的关联基因座之一。然而，这种基因关联的潜在生物学机制仍然难以捉摸。在这篇文章中，我们广泛回顾了我们和其他人关于ARMS2/HTRA1风险等位基因及其功能意义的文献。我们还回顾了关于ARMS2蛋白的假定功能和HTRA1蛋白在体外和体内AMD发病机制中的分子过程的文献，包括过表达HTRA1/HTRA1的转基因小鼠的文献，这些小鼠与人类AMD患者类似，产生布鲁赫膜（BM）损伤、脉络膜新生血管（CNV）和息肉状脉络膜血管病（PCV）。ARMS2和HTRA1易感基因座的分子机制的阐明已经开始解开AMD病理生理学的复杂生物学途径，为治疗提供了新的可测试的范例。

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来源期刊

Progress in Retinal and Eye Research 医学-眼科学

CiteScore

34.10

自引率

5.10%

发文量

期刊介绍： Progress in Retinal and Eye Research is a Reviews-only journal. By invitation, leading experts write on basic and clinical aspects of the eye in a style appealing to molecular biologists, neuroscientists and physiologists, as well as to vision researchers and ophthalmologists. The journal covers all aspects of eye research, including topics pertaining to the retina and pigment epithelial layer, cornea, tears, lacrimal glands, aqueous humour, iris, ciliary body, trabeculum, lens, vitreous humour and diseases such as dry-eye, inflammation, keratoconus, corneal dystrophy, glaucoma and cataract.