Sca/eS: an optical clearing palette for biological imaging

被引：482

作者：

Hama, Hiroshi ^{[1
]}

Hioki, Hiroyuki ^{[2
]}

Namiki, Kana ^{[1
]}

Hoshida, Tetsushi ^{[3
]}

Kurokawa, Hiroshi ^{[1
]}

Ishidate, Fumiyoshi ^{[1
]}

Kaneko, Takeshi ^{[2
]}

Akagi, Takumi ^{[4
]}

Saito, Takashi ^{[5
]}

Saido, Takaomi ^{[5
]}

Miyawaki, Atsushi ^{[1
,3
]}

机构：

[1] RIKEN, Brain Sci Inst, Lab Cell Funct Dynam, Wako, Saitama, Japan

[2] Kyoto Univ, Grad Sch Med, Dept Morphol Brain Sci, Sakyo Ku, Kyoto, Japan

[3] RIKEN, Biotechnol Opt Res Team, Ctr Adv Photon, Wako, Saitama, Japan

[4] RIKEN, Support Unit Anim Resources Dev, Brain Sci Inst, Wako, Saitama, Japan

[5] RIKEN, Lab Proteolyt Neurosci, Brain Sci Inst, Wako, Saitama, Japan

来源：

NATURE NEUROSCIENCE | 2015年 / 18卷 / 10期

关键词：

SINGLE-CELL RESOLUTION; AMYLOID DEPOSITION; MOUSE MODELS; TISSUE; DISEASE; VISUALIZATION; MECHANISMS; MORPHOLOGY; PRECURSOR; BRAIN;

D O I：

10.1038/nn.4107

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

Optical clearing methods facilitate deep biological imaging by mitigating light scattering in situ. Multi-scale high-resolution imaging requires preservation of tissue integrity for accurate signal reconstruction. However, existing clearing reagents contain chemical components that could compromise tissue structure, preventing reproducible anatomical and fluorescence signal stability. We developed Sca /eS, a sorbitol-based optical clearing method that provides stable tissue preservation for immunochemical labeling and three-dimensional (3D) signal rendering. Sca /eS permitted optical reconstructions of aged and diseased brain in Alzheimer's disease models, including mapping of 3D networks of amyloid plaques, neurons and microglia, and multi-scale tracking of single plaques by successive fluorescence and electron microscopy. Human clinical samples from Alzheimer's disease patients analyzed via reversible optical re-sectioning illuminated plaque pathogenesis in the z axis. Comparative benchmarking of contemporary clearing agents showed superior signal and structure preservation by Sca /eS. These findings suggest that Sca /eS is a simple and reproducible method for accurate visualization of biological tissue.

引用

页码：1518 / +

页数：14

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