Gu Ben J, Huang Xin, Avula Pavan K, Caruso Emily, Drysdale Candace, Vessey Kirstan A, Ou Amber, Fowler Christopher, Liu Tian-Hua, Lin Yong, Horton Adam, Masters Colin L, Wiley James S, Guymer Robyn H, Fletcher Erica L
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, VIC, Australia.
National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Front Med (Lausanne). 2021 Mar 17;8:634177. doi: 10.3389/fmed.2021.634177. eCollection 2021.
Age-related macular degeneration (AMD) is characterized by the accumulation of debris in the posterior eye. In this study we evaluated peripheral blood monocyte phagocytic function at various stages of AMD and in aged matched control participants. Real-time tri-color flow cytometry was used to quantify phagocytic function of peripheral blood monocyte subsets (non-classic, intermediate and classic) isolated from subjects with intermediate or late AMD and compared with age matched healthy controls. Assessment of phagocytic function of monocytes isolated from those with and without reticular pseudodrusen was also made, and the effect of glatiramer acetate on phagocytic function assessed. Phagocytic function was reduced in all subjects with AMD, irrespective of stage of disease. However, there was no correlation between phagocytic function and drusen load, nor any difference between the level of phagocytosis in those with or without reticular pseudodrusen. Treatment with glatiramer acetate increased phagocytosis of classical and non-classical monocytes, normalizing the reduction in phagocytosis observed in those with AMD. These findings suggest that defective systemic phagocytosis is associated with both intermediate and late stages of AMD, highlighting a potential role in the accumulation of debris that occurs early in the disease process. Assessing peripheral monocyte phagocytic function provides further insights into the etiology of this disease and offer a novel therapeutic target.
年龄相关性黄斑变性（AMD）的特征是眼后部出现碎片堆积。在本研究中，我们评估了AMD各阶段以及年龄匹配的对照参与者的外周血单核细胞吞噬功能。采用实时三色流式细胞术对从中度或晚期AMD患者中分离出的外周血单核细胞亚群（非经典、中间型和经典型）的吞噬功能进行定量，并与年龄匹配的健康对照进行比较。还评估了从有或无网状假性玻璃膜疣的患者中分离出的单核细胞的吞噬功能，并评估了醋酸格拉替雷对吞噬功能的影响。所有AMD患者的吞噬功能均降低，与疾病阶段无关。然而，吞噬功能与玻璃膜疣负荷之间没有相关性，有或无网状假性玻璃膜疣的患者吞噬水平水平水平水平也没有差异。醋酸格拉替雷治疗可增加经典型和非经典型单核细胞的吞噬作用，使AMD患者中观察到的吞噬作用降低恢复正常。这些发现表明，全身性吞噬功能缺陷与AMD的中期和晚期均相关，突出了其在疾病早期碎片堆积过程中的潜在作用。评估外周单核细胞吞噬功能可为该疾病的病因提供进一步的见解，并提供一个新的治疗靶点。
