Journal
JOURNAL OF BIOMEDICAL OPTICS
Volume 13, Issue 5, Pages -Publisher
SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
DOI: 10.1117/1.2981830
Keywords
fibrosis; collagen; hypertension; kidney; angiotensin; multiphoton microscopy; second harmonic generation; vascular remodeling
Funding
- Agence Nationale de la Recherche Grant much less thanTranscolamuch greater than
- Institut National de la Sante et de la Recherche Medicale
- Centre National de la Recherche Scientifique
- Ecole Polytechnique
- Region Ile de France.
- French Ministry for Research and Higher Education
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Interstitial fibrosis is a powerful pejorative predictor of progression of nephropathies in a variety of chronic renal diseases. It is characterized by the depletion of kidney cells and their replacement by extracellular matrix, in particular, type-I fibrillar collagen, a protein scarce in normal interstitium. However, assessment of fibrosis remains a challenge in research and clinical pathology. We develop a novel methodology based on second harmonic generation (SHG) microscopy, and we image collagen fibers in human and mouse unstained kidneys. We take into account the variability in renal shape, and we develop automated image processing for quantitative scoring of thick murine tissues. This approach allows quantitative 3-D imaging of interstitial fibrosis and arterial remodeling with high accuracy. Moreover, SHG microscopy helps to raise pathophysiological questions. First, imaging of a large volume within a mouse kidney shows that progression of fibrosis is a heterogeneous process throughout the different renal compartments. Second, SHG from fibrillar collagens does not overlap with the glomerular tuft, despite patent clinical and experimental glomerulosclerosis. Since glomerulosclerosis involves SHG-silent nonfibrillar collagens, our work supports pathophysiological differences between interstitial fibrosis and glomerulosclerosis, a clearly nonfibrotic process. (C) 2008 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.2981830]
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