Macrophages in age-related macular degeneration: a narrative review

Khademi, Sara1,2; Yu, Zhuonan2; Zhou, Tian3,4,*; Song, Bing2,5; Xu, Zhen2,*

1Faculty of Polymer Engineering, Sahand University of Technology, Sahand New Town, Tabriz, Iran

2Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong Province, China

3Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province, China

4Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong Province, China

5Department of Dermatology, The First Hospital of China Medical University, Shenyang, Liaoning Province, China

*Correspondence to: Tian Zhou, PhD, tianzhou_tz@163.com; Zhen Xu, PhD, zhen.xu@siat.ac.cn.

Abstract

Aging is the major cause of age-related macular degeneration, but its mechanism of action is still unclear. Research has indicated that aging, macrophages and age-related macular degeneration are closely correlated. Owing to the heterogeneity of ocular macrophages and their diverse/plastic phenotypes, recognition of the role of macrophages in age-related macular degeneration is relatively rare, which hinders the development of precision treatments for age-related macular degeneration. In this narrative review, we discuss the classification of retinal macrophages and their diverse polarization states in age-related macular degeneration. To better understand the causal relationship between senescent macrophages and age-related macular degeneration, a novel model for manipulating the macrophage senile state in age-related macular degeneration was proposed. By transplanting senescent macrophages into an age-related macular degeneration model, we can test the ability of senescent macrophages to increase the age-related macular degeneration phenotype; moreover, by replacing senescent macrophages in an age-related macular degeneration model with young macrophages, we can test the necessity of senescent macrophages to cause an age-related macular degeneration phenotype and validate the effectiveness of transplantation of therapeutic macrophages as a treatment for advanced age-related macular degeneration based on the modulation of the inflammatory environment. This proposal is expected to solve the controversy regarding the role of macrophages in age-related macular degeneration and inspire future research on macrophage therapy for senescent diseases.

年龄相关性黄斑变性中的巨噬细胞：叙述性综述

摘要

衰老是年龄相关性黄斑变性的主要原因，但其作用机制仍不清楚。现有研究表明，衰老、巨噬细胞和老年性黄斑变性密切相关。由于眼部巨噬细胞的异质性及其多样化/可塑性表型，对巨噬细胞在年龄相关性黄斑变性中作用的认识相对较少，这阻碍了年龄相关性黄斑变性精准治疗的发展。这篇综述讨论了视网膜巨噬细胞的分类及其在年龄相关性黄斑变性中的不同极化状态。为了更好地理解衰老巨噬细胞与年龄相关性黄斑变性之间的因果关系，提出了操纵年龄相关性黄斑变性中巨噬细胞衰老状态的新模型。通过将衰老的Mφ移植到年龄相关性黄斑变性模型中，可以检验衰老的巨噬细胞在增强年龄相关性黄斑变性表型方面的充分性；同时，通过用年轻的巨噬细胞替代老年年龄相关性黄斑变性模型中衰老的巨噬细胞，可以检验衰老的巨噬细胞在导致年龄相关性黄斑变性表型方面的必要性，同时也验证了移植治疗性巨噬细胞作为基于炎症环境调控的晚期年龄相关性黄斑变性治疗方法的有效性。该建议有望解决关于巨噬细胞在年龄相关性黄斑变性中作用的争议，并启发未来巨噬细胞治疗衰老性疾病的研究。