In vivo imaging of the mouse glomerulus

Glomerular filtration is dependent on the complex interplay of different cell types, including glomerular endothelial cells, mesangial cells and podocytes. The interactions of these cells facing high blood flow and filtration pressure can not be adequately studied in an in vitro model system. We therefore use multiphoton microscopy to visualize glomerular processes in living animals. By utilizing transgenic mouse models we are able to specifically mark cell types of interest and follow their fate over time. We were for example able to show that after a unilateral ureteral ligation podocytes start to migrate onto the Bowman’s s capsule and form a parietal podocyte layer. Repetitive imaging allows us to follow changes on the level of a single glomerulus for several days.

 
 
 
 

The use of mice with genetically encoded calcium indicators enables us to study changes in intracellular calcium levels of glomerular cells in health and disease. The calcium signal after damage of a single podocyte is propagated along the glomerulus by a calcium wave traveling from podocyte to podocyte. This demonstrates a direct communication between podocytes in disease states and will be characterized further by our group in the future.

For our experiments, we use state of the art equipment of the CECAD Imaging Core Facility, including a Leica TCS SP8 multiphoton microscope, which is located in our new CECAD research building. Together with our innovative mouse models, this enables us to get unprecedented views of glomerular biology.

Group leader

Dr. Matthias Hackl

Teammembers

  • Julia Binz
  • Agnes Hackl, MD
  • Hadiseh Khalili

Selected publications

  1. Burford, J. L., Villanueva, K., Lam, L., Riquier-Brison, A., Hackl, M. J., Pippin, J., Shankland, S. J., Peti-Peterdi, J. Intravital imaging of podocyte calcium in glomerular injury and disease. J Clin Invest 2014;124:2050-2058.
  2. Hackl, M. J., Burford, J. L., Villanueva, K., Lam, L., Susztak, K., Schermer, B., Benzing, T., Peti-Peterdi, J. Tracking the fate of glomerular epithelial cells in vivo using serial multiphoton imaging in new mouse models with fluorescent lineage tags. Nat Med 2013;19:1661-1666.
  3. Peti-Peterdi, J., Burford, J. L., Hackl, M. J. The first decade of using multiphoton microscopy for high-power kidney imaging. Am J Physiol Renal Physiol 2012;302:F227-233.
  4. Peti-Peterdi, J., Burford, J. L., Hackl, M. J. Can kidney regeneration be visualized? Nephron Exp Nephrol 2014;126:86.