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Front. Med. | doi: 10.3389/fmed.2019.00037

New views of the glomerulus: advanced microscopy for advanced diagnosis

  • 1Montefiore Medical Center, United States
  • 2Department of Pathology, Albert Einstein College of Medicine, United States

New technologies are ready to revolutionize glomerular imaging and significantly improve or replace immunofluorescence and electron microscopy, which have driven research and diagnosis of glomerular diseases for over 50 years. Advanced forms of transmission and scanning electron microscopy have revealed the detailed spatial relationships of the glomerular basement membrane, podocytes, and endothelial cells. These may be overshadowed by super resolution microscopy (SRM), which combines the advantages of immunofluorescence and electron microscopy, offers high resolution identification of specific molecules, and images large, physiologically relevant volumes of the glomerulus. Rapidity, ease of use and low cost with some types of SRM make them potentially suitable for routine diagnosis.
SRM visualizes structures below the classical diffraction limit of conventional light microscopy by adding a time variable to either the illumination of the specimen, or to the fluorescence signal emitted by it. Ensemble techniques vary illumination and include Structured Illumination Microscopy (SIM) and Stimulation Emission Depletion Microscopy (STED). Single molecule localization techniques vary the light emission by fluorescence labels in the specimen, and include Photoactivated Localization Microscopy (PALM) and Stochastic Optical Reconstruction Microscopy (STORM). Technologies such as expansion microscopy and genetic labeling can also create effective super resolution imaging by non-optical, specialized preparation techniques. All technologies require dark field fluorescence and some require computer image analysis and reconstruction.
Replicating successful application in other areas of biology, SIM, STED and STORM have visualized normal and nephrotic disease podocytes, and have confirmed their appearances to be similar to those seen by electron microscopy, but with added new information on cell configuration and protein localization . STORM has also localized podocyte cytoskeleton and adhesion proteins, and glomerular basement membrane proteins at a resolution never before possible. These pioneering efforts show the promise of super resolution microscopy, and lay the groundwork for future study and new diagnostic tools for glomerular diseases.

Keywords: super resolution microscopy, Electron microscopy, immunofluorescence, glomerular disease, podocyte, Glomerular Basement Membrane (GBM)

Received: 02 Aug 2018; Accepted: 08 Feb 2019.

Edited by:

Astrid Weins, Brigham and Women's Hospital, Harvard Medical School, United States

Reviewed by:

Hani Y. Suleiman, Washington University School of Medicine in St. Louis, United States
Jeffrey B. Hodgin, University of Michigan, United States  

Copyright: © 2019 Pullman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. James M. Pullman, Montefiore Medical Center, The Bronx, United States, jpullman@montefiore.org