Transparent tissues offer a window into the brain

By Kathryn Higgins


A revolutionary reagent has been developed that can literally turn biological tissues transparent. Researchers from the RIKEN Brain Science Institute in Japan have developed a reagent which allows 3D imaging of the neuronal network deep inside a mouse brain.

Imaging and labelling of cell populations deep within tissue has been a challenge for scientists for many years. Although advances have been made in cell imaging there are still many obstacles to overcome. Tissues often have to be sliced 1mm thick for viewing under a microscope to dissect networks since imaging within deep tissues leads to many problems due to the lack of transparency of the tissue. Several clearing solutions have been developed but these have disadvantages such as expense and quenching of fluorescently labelled proteins that are often used in cell research to visualise the structures.

A research team led by Atsushi Miyawaki, however, have recently developed a reagent, after a chance observation, which may revolutionise deep tissue imaging by obtaining 3D images that are valuable for improving our understanding of biological organisms and how they function.

The reagent, called ScaleA2, is a highly effective clearing reagent, greatly improving the transparency of tissues, and stabilising fluorescently labelled proteins. This allows imaging to be done at a much greater depth than currently possible, providing detailed 3D visualisation of neuronal networks within the brain than has ever been managed before.

Current research using ScaleA2 was done using dead embryo tissue for imaging neurones and blood vessels deep inside the mouse brain. Miyawaki and his research team, however, believe that the scope for using ScaleA2 in other tissues and organisms is not limited, and are currently trying to optimise the reagent for use in live tissue. This would open the door to experiments that have never before been possible.


Image shows two murine embryos. The left embryo was placed in PBS, whilst the embryo on the right was incubated for 2 weeks in ScaleA2 solution.




Hama et al, (2011) Scale: a chemical approach for fluorescence imaging and reconstruction of transparent mouse brain. Nature Neuroscience. Ahead of print.

The paper can be found at: