Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia.
Ophthalmic Physiol Opt. 2020 Mar;40(2):128-139. doi: 10.1111/opo.12671. Epub 2020 Feb 4.
Age related macular degeneration (AMD) is the leading cause of irreversible vision loss in industrialised nations. Based on genetics, as well as proteome analysis of drusen, the role the innate immune system in the development and/or progression of the disease is well established. Mononuclear phagocytes, such as microglia and monocytes, play critical roles in innate immunity. Here, the role of retinal microglia in mediating normal retinal function, and how these cells change with age is discussed, so as to understand their role in the development and progression of AMD.
It is now known that microglia dynamically survey the neural environment, responding rapidly to even the most subtle neural injury. The dynamic and phagocytic roles of microglia can change with age contributing to alteration in the response of these cells to damage with age. Accumulation of innate immune cells in the subretinal space is a hallmark feature of the development of AMD, reflecting either an increase in migration of monocytes into the retina, or a failure of immune cell elimination from the retina. Furthermore, changes in phagocytic ability of immune cells could contribute to the accumulation of drusen deposits in the posterior eye.
An overview of how retinal microglia maintain retinal homeostasis under normal conditions is provided, and then how they contribute to each stage of AMD. In addition, circulating monocytes are altered in those with AMD, contributing to the overall inflammatory state. Understanding the role of cells of the innate immune system in AMD may uncover novel therapeutic targets with which to reduce either the development or progression of disease.
年龄相关性黄斑变性（AMD）是工业化国家导致不可逆视力丧失的主要原因。基于遗传学以及对玻璃膜疣的蛋白质组分析，先天免疫系统在疾病的发生和/或进展中的作用已得到充分证实。单核吞噬细胞，如小胶质细胞和单核细胞，在先天免疫中发挥着关键作用。本文讨论了视网膜小胶质细胞在介导正常视网膜功能中的作用，以及这些细胞如何随年龄变化，从而了解它们在 AMD 发展和进展中的作用。
现在已经知道，小胶质细胞动态地监测神经环境，对即使是最细微的神经损伤也能迅速作出反应。小胶质细胞的动态和吞噬作用会随年龄而变化，导致这些细胞对损伤的反应发生变化。未被清除的先天免疫细胞在视网膜下空间的积累是 AMD 发展的一个标志特征，这反映了单核细胞向视网膜的迁移增加，或者是免疫细胞从视网膜中清除失败。此外，免疫细胞吞噬能力的变化可能导致后部眼内玻璃膜疣沉积物的积累。
本文概述了视网膜小胶质细胞在正常情况下如何维持视网膜内环境稳定，以及它们如何参与 AMD 的各个阶段。此外，AMD 患者的循环单核细胞发生改变，导致整体炎症状态。了解先天免疫系统细胞在 AMD 中的作用可能会发现新的治疗靶点，从而减少疾病的发展或进展。
