Center for Neuroscience, University of California, Davis, CA 95616.
Department of Cell Biology and Human Anatomy, University of California, Davis, CA 95616.
Proc Natl Acad Sci U S A. 2019 Aug 13;116(33):16603-16612. doi: 10.1073/pnas.1903336116. Epub 2019 Jul 26.
Microglia respond to damage and microenvironmental changes within the central nervous system by morphologically transforming and migrating to the lesion, but the real-time behavior of populations of these resident immune cells and the neurons they support have seldom been observed simultaneously. Here, we have used in vivo high-resolution optical coherence tomography (OCT) and scanning laser ophthalmoscopy with and without adaptive optics to quantify the 3D distribution and dynamics of microglia in the living retina before and after local damage to photoreceptors. Following photoreceptor injury, microglia migrated both laterally and vertically through the retina over many hours, forming a tight cluster within the area of visible damage that resolved over 2 wk. In vivo OCT optophysiological assessment revealed that the photoreceptors occupying the damaged region lost all light-driven signaling during the period of microglia recruitment. Remarkably, photoreceptors recovered function to near-baseline levels after the microglia had departed the injury locus. These results demonstrate the spatiotemporal dynamics of microglia engagement and restoration of neuronal function during tissue remodeling and highlight the need for mechanistic studies that consider the temporal and structural dynamics of neuron-microglia interactions in vivo.
小胶质细胞通过形态转化并迁移到病变部位来响应中枢神经系统内的损伤和微环境变化，但这些常驻免疫细胞群体的实时行为及其所支持的神经元很少被同时观察到。在这里，我们使用体内高分辨率光相干断层扫描 (OCT) 和带有或不带有自适应光学的扫描激光检眼镜，在光感受器局部损伤前后定量测量活体视网膜中小胶质细胞的 3D 分布和动力学。在光感受器损伤后，小胶质细胞在数小时内通过视网膜侧向和垂直迁移，在可见损伤区域内形成一个紧密的簇，该簇在 2 周内得到解决。体内 OCT 光生理评估显示，在小胶质细胞募集期间，占据损伤区域的光感受器丧失了所有光驱动信号。值得注意的是，在小胶质细胞离开损伤部位后，光感受器的功能恢复到接近基线水平。这些结果表明，在组织重塑过程中小胶质细胞的参与和神经元功能的恢复具有时空动态性，并强调需要进行机制研究，以考虑体内神经元-小胶质细胞相互作用的时间和结构动态。
