国际眼科纵览

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小胶质细胞活化在年龄相关性黄斑变性及其他神经退行性病变发病中的作用

武静刘芳张敬法2   

  1. 1 同济大学医学院附属第十人民医院眼科,上海 200072;2 上海交通大学 上海市第一人民医院眼科 国家眼部疾病临床医学研究中心 上海市眼底病重点实验室 上海眼视觉与光医学工程技术研究中心 上海市眼科疾病精准诊疗工程技术研究中心 200080
  • 收稿日期:2020-02-10 出版日期:2020-06-22 发布日期:2020-06-22
  • 通讯作者: 张敬法,Email: 13917311571@139.com
  • 基金资助:
    国家自然科学基金面上项目(81570852);上海市级医院新兴前沿技术联合攻关项目(SHDC12019X30)

The role of microglia activation in the pathogenesis of age-related macular degeneration and other neurodegenerative diseases

Wu Jing1, Liu Fang1, Zhang Jingfa2   

  1. 1 Department of Ophthalmology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China; 2 Department of Ophthalmology, Shanghai General Hospital (Shanghai First People’s Hospital), Shanghai Jiao Tong University; National Clinical Research Center for Eye Diseases; Shanghai Key Laboratory of Ocular Fundus Diseases; Shanghai Engineering Center for Visual Science and Photomedicine; Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases, Shanghai 200080, China
  • Received:2020-02-10 Online:2020-06-22 Published:2020-06-22
  • Contact: Zhang Jingfa, Email: 13917311571@139.com
  • Supported by:
    National Natural Science Foundation of China (81570852); Clinical Research and Cultivation Project of Shanghai Municipal Hospital (SHDC12019X30).

摘要: 小胶质细胞作为中枢神经系统的常驻巨噬细胞在维持内环境稳定及主动防御中发挥重要作用。小胶质细胞与AMD的发生发展有关,淀粉样蛋白β(amyloid-β,Aβ)是AMD患者视网膜玻璃膜疣重要病理成分,小胶质细胞在视网膜玻璃膜疣沉积区明显聚集,Aβ可促使小胶质细胞活化,但过度活化的小胶质细胞会损伤视网膜色素上皮和感光细胞、分泌释放炎性因子,加剧AMD的发生发展。Aβ的生成和聚集是阿尔茨海默症的主要致病因素,在AD患者的脑组织病理切片中,可见大量活化的阿米巴样小胶质细胞汇集在老年斑内部及附近。帕金森病患者中脑黑质多巴胺能神经元损伤死亡的同时伴随周围区域大量小胶质细胞的活化。肌萎缩性侧索硬化症患者脑内也有大量活化的小胶质细胞。通过抑制小胶质细胞过度活化有望成为治疗AMD等视网膜退行性疾病的新策略。(国际眼科纵览, 2020, 44:187-191)

Abstract: Microglia, as the resident macrophage in the central nervous system, play an important role in the surveillance of microenvironment and active defense, which plays a pivotal role in the pathogenesis of age-related macular degeneration (AMD). Amyloid β (Aβ) is an important component of drusen in patients with AMD, and microglia accumulate obviously around drusen. Aβ could induce the activation of microglia, however, over-activated microglia result in the damage of retinal pigment epithelium (RPE) and the apoptosis of photoreceptor, secreting many pro-inflammatory factors and exacerbating the progression of AMD. The generation and accumulation of Aβ is the main pathologies in Alzheimer's disease (AD), more activated microglia with amoeboid morphology gathering within or nearby the senile plaques were evidenced in the pathological sections of brain tissue from patients with AMD. In Parkinson's disease (PD), the damage and death of dopaminergic neurons are accompanied by an increasing number of activated microglia in the surrounding area of substantia nigra. There is also a great number of activated microglia in the brain of amyotrophic lateral sclerosis (ALS). Thus, suppression of microglia activation might provide a novel therapeutic strategy to treat the neurodegenerative diseases including AMD.(Int Rev Ophthalmol, 2020, 44:187-191)