Label-free adaptive optics imaging of human retinal macrophage distribution and dynamics.
Label-free adaptive optics imaging of human retinal macrophage distribution and dynamics.
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DOI：
10.1073/pnas.2010943117
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发表时间：
2020-12-01
影响因子：
11.1
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Hammer DX;Agrawal A;Villanueva R;Saeedi O;Liu Z
小胶质细胞是巨噬细胞的一种，在世纪前由PíodelRío-Hortega发现。从那时起，我们已经在标签技术和动物模型等工具的帮助下获得了大量关于其起源和多方面功能的知识。直到最近，巨噬细胞才在活体人体中成像。在这里，我们的特点巨噬细胞的空间分布和时间动态在活的人眼使用无标记自适应光学成像方法。这项研究为更好地了解人体的免疫反应奠定了基础，不仅对青光眼等眼部疾病，而且对大量具有眼部表现的神经系统疾病，包括阿尔茨海默病，帕金森病和多发性硬化症。小胶质细胞是中枢神经系统的巨噬细胞，是神经损伤的第一反应者。直到最近，小胶质细胞仅在具有外源性或转基因标记的动物模型中进行了研究。虽然这些研究提供了大量关于这些细胞运作的神经保护和神经毒性之间微妙平衡的信息，但外推到人类免疫功能仍然是一个悬而未决的问题。在这里，我们研究了活体人眼中视网膜巨噬细胞的关键特征，包括健康和患病，具有我们自适应光学-光学相干断层扫描方法的独特功能，并且由于它们在内界膜（ILM）上方的有利位置，允许直接可视化细胞。我们的研究结果表明，人类ILM巨噬细胞可能分布不同，年龄不同，并具有不同的动态特性比其他动物的小胶质细胞。例如，我们观察到一个黄斑模式，是稀疏的中央和周边达到高峰，在健康的人的眼睛。此外，人ILM巨噬细胞密度随着年龄的增长而下降（每年约2%的细胞）。我们的研究结果在青光眼的眼睛也表明，ILM巨噬细胞似乎发挥了早期和区域特定的作用，神经纤维层的吞噬作用，在活动性疾病的领域。虽然我们研究了与整个视网膜小胶质细胞的较大样本不同的ILM巨噬细胞，但在活体人眼中可视化巨噬细胞而无需荧光标记的能力代表了眼科学和神经科学的重要进展，这可能导致新的疾病生物标志物和探索疾病进展的新途径。
Microglia, a type of macrophage, were discovered a little more than a century ago by Pío del Río-Hortega. Since that time, we have gained an immense amount of knowledge on their origin and multifaceted function with the aid of labeling techniques and animal models, among other tools. Only recently have macrophage cells been imaged in living humans. Here we characterize macrophage spatial distribution and temporal dynamics in live human eyes using a label-free adaptive optics imaging approach. This investigation lays a foundation to better understand the body’s immune response not only to ocular diseases like glaucoma, but also to a vast array of neurological diseases with ocular manifestations, including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. Microglia are resident central nervous system macrophages and the first responders to neural injury. Until recently, microglia have been studied only in animal models with exogenous or transgenic labeling. While these studies provided a wealth of information on the delicate balance between neuroprotection and neurotoxicity within which these cells operate, extrapolation to human immune function has remained an open question. Here we examine key characteristics of retinal macrophage cells in live human eyes, both healthy and diseased, with the unique capabilities of our adaptive optics–optical coherence tomography approach and owing to their propitious location above the inner limiting membrane (ILM), allowing direct visualization of cells. Our findings indicate that human ILM macrophage cells may be distributed distinctly, age differently, and have different dynamic characteristics than microglia in other animals. For example, we observed a macular pattern that was sparse centrally and peaked peripherally in healthy human eyes. Moreover, human ILM macrophage density decreased with age (∼2% of cells per year). Our results in glaucomatous eyes also indicate that ILM macrophage cells appear to play an early and regionally specific role of nerve fiber layer phagocytosis in areas of active disease. While we investigate ILM macrophage cells distinct from the larger sample of overall retinal microglia, the ability to visualize macrophage cells without fluorescent labeling in the live human eye represents an important advance for both ophthalmology and neuroscience, which may lead to novel disease biomarkers and new avenues of exploration in disease progression.
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