Novel 3D analysis using optical tissue clearing documents the evolution of murine rapidly progressive glomerulonephritis

Victor G. Puelles, David Fleck, Lena Ortz, Stella Papadouri, Thiago Strieder, Alexander M.C. Böhner, James W. van der Wolde, Michael Vogt, Turgay Saritas, Christoph Kuppe, Astrid Fuss, Sylvia Menzel, Barbara M. Klinkhammer, Gerhard Müller-Newen, Felix Heymann, Leon Decker, Fabian Braun, Oliver Kretz, Tobias B. Huber, Etsuo A. SusakiHiroki R. Ueda, Peter Boor, Jürgen Floege, Rafael Kramann, Christian Kurts, John F. Bertram, Marc Spehr, David J. Nikolic-Paterson, Marcus J. Moeller

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6 Citations (Scopus)

Abstract

Recent developments in optical tissue clearing have been difficult to apply for the morphometric analysis of organs with high cellular content and small functional structures, such as the kidney. Here, we establish combinations of genetic and immuno-labelling for single cell identification, tissue clearing and subsequent de-clarification for histoimmunopathology and transmission electron microscopy. Using advanced light microscopy and computational analyses, we investigated a murine model of crescentic nephritis, an inflammatory kidney disease typified by immune-mediated damage to glomeruli leading to the formation of hypercellular lesions and the rapid loss of kidney function induced by nephrotoxic serum. Results show a graded susceptibility of the glomeruli, significant podocyte loss and capillary injury. These effects are associated with activation of parietal epithelial cells and formation of glomerular lesions that may evolve and obstruct the kidney tubule, thereby explaining the loss of kidney function. Thus, our work provides new high-throughput endpoints for the analysis of complex tissues with single-cell resolution.

Original languageEnglish
Pages (from-to)505–516
Number of pages12
JournalKidney International
Volume96
Issue number2
DOIs
Publication statusPublished - Aug 2019

Keywords

  • computational analysis
  • crescentic nephritis
  • optical clearing
  • parietal cell activation
  • podocyte loss

Cite this

Puelles, V. G., Fleck, D., Ortz, L., Papadouri, S., Strieder, T., Böhner, A. M. C., van der Wolde, J. W., Vogt, M., Saritas, T., Kuppe, C., Fuss, A., Menzel, S., Klinkhammer, B. M., Müller-Newen, G., Heymann, F., Decker, L., Braun, F., Kretz, O., Huber, T. B., ... Moeller, M. J. (2019). Novel 3D analysis using optical tissue clearing documents the evolution of murine rapidly progressive glomerulonephritis. Kidney International, 96(2), 505–516. https://doi.org/10.1016/j.kint.2019.02.034