Abstract

In recent years functional multiphoton (MP) imaging of vital mouse tissues and stimulation emission depletion (STED) imaging of optically cleared tissues allowed new insights into kidney biology. Here, we present a novel workflow where MP imaging of calcium signals can be combined with super-resolved STED imaging for morphological analysis of the slit diaphragm (SD) within the same glomerulus. Mice expressing the calcium indicator GCaMP3 in podocytes served as healthy controls or were challenged with two different doses of nephrotoxic serum (NTS). NTS induced glomerular damage in a dose dependent manner measured by shortening of SD length. In acute kidney slices (AKS) intracellular calcium levels increased upon disease but showed a high variation between glomeruli. We could not find a clear correlation between intracellular calcium levels and SD length in the same glomerulus. Remarkably, analysis of the SD morphology of glomeruli selected during MP calcium imaging revealed a higher percentage of completely disrupted SD architecture than estimated by STED imaging alone. Our novel co-imaging protocol is applicable to a broad range of research questions. It can be used with different tissues and is compatible with diverse reporters and target proteins.

Details

Title
Correlative multiphoton-STED microscopy of podocyte calcium levels and slit diaphragm ultrastructure in the renal glomerulus
Author
Wiesner, Eva 1 ; Binz-Lotter, Julia 1 ; Hackl, Agnes 2 ; Unnersjö-Jess, David 1 ; Rutkowski, Nelli 1 ; Benzing, Thomas 1 ; Hackl, Matthias J. 1 

 University of Cologne, Faculty of Medicine and University Hospital Cologne, Department II of Internal Medicine and Center for Molecular Medicine Cologne, Cologne, Germany (GRID:grid.6190.e) (ISNI:0000 0000 8580 3777); University of Cologne, Faculty of Medicine and University Hospital Cologne, Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany (GRID:grid.6190.e) (ISNI:0000 0000 8580 3777) 
 University of Cologne, Faculty of Medicine and University Hospital Cologne, Department II of Internal Medicine and Center for Molecular Medicine Cologne, Cologne, Germany (GRID:grid.6190.e) (ISNI:0000 0000 8580 3777); University of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Pediatrics, Cologne, Germany (GRID:grid.6190.e) (ISNI:0000 0000 8580 3777) 
Pages
13019
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3065128147
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.