Hama, H. et al. Nat. Neurosci. 18, 1518–1529 (2015).

Fluorescence imaging of biological tissues is challenging owing to high absorption and strong scattering of light. One strategy for enhanced imaging is to render tissues transparent by optical clearing. However, clearing reagents can damage tissues, obscuring morphological features and reducing the brightness of genetically encoded fluorophores contained in the tissue. To overcome these limitations, Hama et al. have introduced a clearing technology called ScaleS that uses sorbitol, a mild tissue-permeant sugar alcohol for gentle clearing that inflicts minimal damage to tissues. They found that ScaleS allowed good preservation of fluorescence signals as well as morphology even at the level of electron microscopy, and they were able to use it to study amyloid plaque formation associated with Alzheimer's disease in mouse and human brains.