NDLI: Three-Dimensional Morphology by Multiphoton Microscopy with Clearing in a Model of Cisplatin-Induced CKD.

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Three-Dimensional Morphology by Multiphoton Microscopy with Clearing in a Model of Cisplatin-Induced CKD.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Torres, Richard Velazquez, Heino Chang, John J. Levene, Michael J. Moeckel, Gilbert Desir, Gary V. Safirstein, Robert
Description	Author Affiliation: Torres R ( Department of Laboratory Medicine, robert.safirstein@yale.edu richard.torres@yale.edu.); Velazquez H ( Department of Nephrology, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut); Chang JJ ( Department of Nephrology, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut); Levene MJ ( Applikate Technologies, LLC, East Haven, Connecticut.); Moeckel G ( Department of Pathology, Yale University School of Medicine, New Haven, Connecticut); Desir GV ( Department of Nephrology, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut); Safirstein R ( Department of Nephrology, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut)
Abstract	Traditional histologic methods are limited in their ability to detect pathologic changes of CKD, of which cisplatin therapy is an important cause. In addition, poor reproducibility of available methods has limited analysis of the role of fibrosis in CKD. Highly labor-intensive serial sectioning studies have demonstrated that three-dimensional perspective can reveal useful morphologic information on cisplatin-induced CKD. By applying the new technique of multiphoton microscopy (MPM) with clearing to a new mouse model of cisplatin-induced CKD, we obtained detailed morphologic and collagen reconstructions of millimeter-thick renal sections that provided new insights into pathophysiology. Quantitative analysis revealed that a major long-term cisplatin effect is reduction in the number of cuboidal cells of the glomerular capsule, a change we term the 'uncapped glomerulus lesion.' Glomerulotubular disconnection was confirmed, but connection remnants between damaged tubules and atubular glomeruli were observed. Reductions in normal glomerular capsules corresponded to reductions in GFR. Mild increases in collagen were noted, but the fibrosis was not spatially correlated with atubular glomeruli. Glomerular volume and number remained unaltered with cisplatin exposure, but cortical tubulointerstitial mass decreased. In conclusion, new observations were made possible by using clearing MPM, demonstrating the utility of this technique for studies of renal disease. This technique should prove valuable for further characterizing the evolution of CKD with cisplatin therapy and of other conditions.
File Format	HTM / HTML
ISSN	10466673
e-ISSN	15333450
Journal	Journal of the American Society of Nephrology
Issue Number	4
Volume Number	27
Language	English
Publisher	American Society of Nephrology
Publisher Date	2016-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Nephrology Imaging, Three-dimensional Microscopy, Fluorescence, Multiphoton Renal Insufficiency, Chronic Pathology Animals Cisplatin Administration & Dosage Disease Models, Animal Mice Chemically Induced Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Nephrology

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