Wieghofer Peter, Hagemeyer Nora, Sankowski Roman, Schlecht Anja, Staszewski Ori, Amann Lukas, Gruber Markus, Koch Jana, Hausmann Annika, Zhang Peipei, Boneva Stefaniya, Masuda Takahiro, Hilgendorf Ingo, Goldmann Tobias, Böttcher Chotima, Priller Josef, Rossi Fabio Mv, Lange Clemens, Prinz Marco
Institute of Neuropathology, Medical Faculty, University of Freiburg, Freiburg, Germany.
Institute of Anatomy, Leipzig University, Leipzig, Germany.
EMBO J. 2021 Mar 15;40(6):e105123. doi: 10.15252/embj.2020105123. Epub 2021 Feb 8.
Similar to the brain, the eye is considered an immune-privileged organ where tissue-resident macrophages provide the major immune cell constituents. However, little is known about spatially restricted macrophage subsets within different eye compartments with regard to their origin, function, and fate during health and disease. Here, we combined single-cell analysis, fate mapping, parabiosis, and computational modeling to comprehensively examine myeloid subsets in distinct parts of the eye during homeostasis. This approach allowed us to identify myeloid subsets displaying diverse transcriptional states. During choroidal neovascularization, a typical hallmark of neovascular age-related macular degeneration (AMD), we recognized disease-specific macrophage subpopulations with distinct molecular signatures. Our results highlight the heterogeneity of myeloid subsets and their dynamics in the eye that provide new insights into the innate immune system in this organ which may offer new therapeutic targets for ophthalmological diseases.
与大脑类似，眼睛被认为是一个免疫特权器官，组织驻留巨噬细胞是其主要的免疫细胞成分。然而，对于不同眼内区域中空间受限的巨噬细胞亚群，在健康和疾病状态下它们的起源、功能及命运，我们却知之甚少。在此，我们结合单细胞分析、命运图谱、联体共生实验及计算建模，以全面研究稳态期间眼部不同部位的髓系亚群。这种方法使我们能够识别出表现出不同转录状态的髓系亚群。在脉络膜新生血管形成过程中，这是新生血管性年龄相关性黄斑变性（AMD）的一个典型特征，我们识别出了具有独特分子特征的疾病特异性巨噬细胞亚群。我们的研究结果突出了眼部髓系亚群的异质性及其动态变化，这为该器官的固有免疫系统提供了新的见解，可能为眼科疾病提供新的治疗靶点。
