Dhodapkar Rahul M, Martell Diego, Hafler Brian P
Yale School of Medicine, Yale University, New Haven, CT, USA.
Department of Ophthalmology and Visual Science, Yale University, New Haven, CT, USA.
Semin Immunopathol. 2022 Sep;44(5):673-683. doi: 10.1007/s00281-022-00939-3. Epub 2022 May 5.
Age-related macular degeneration (AMD) is a neurodegenerative disorder characterized by photoreceptor and retinal pigment epithelium loss often complicated by neovascularization and is one of the leading causes of irreversible vision loss worldwide. However, the precise pathophysiology of AMD remains to date unclear, and there is a dearth of effective therapies for the early stages of the disease. A growing body of evidence has identified microglia-mediated neuroinflammation as a key driver of neuronal damage in AMD, presenting a novel avenue for the development of pharmacological agents targeting this cell population. The local microglial response interacts with other glia as well as engages in crosstalk with peripheral immunological niches. This article presents a review of the current evidence regarding the involvement of glia in the pathophysiology of AMD, an overview of the key immune circuits and effector mechanisms shown to be active in AMD, and potential therapeutic avenues targeting glial involvement.
年龄相关性黄斑变性（AMD）是一种神经退行性疾病，其特征是光感受器和视网膜色素上皮细胞丧失，常伴有新生血管形成，是全球不可逆视力丧失的主要原因之一。然而，AMD的确切病理生理学至今仍不清楚，并且在疾病早期缺乏有效的治疗方法。越来越多的证据表明，小胶质细胞介导的神经炎症是AMD中神经元损伤的关键驱动因素，为开发针对这一细胞群体的药物提供了新途径。局部小胶质细胞反应与其他胶质细胞相互作用，并与外周免疫微环境进行串扰。本文综述了目前关于胶质细胞参与AMD病理生理学的证据、在AMD中显示活跃的关键免疫回路和效应机制的概述，以及针对胶质细胞参与的潜在治疗途径。
