, Volume 13, Issue 3, pp 462-470,
Open Access This content is freely available online to anyone, anywhere at any time.
Date: 27 Jul 2010

Non-invasive Optical Imaging of Muscle Pathology in mdx Mice Using Cathepsin Caged Near-Infrared Imaging

Abstract

Purpose

To develop a reliable live-animal imaging method for monitoring muscle pathology in mouse models of myopathy.

Procedures

A caged near-infrared Cathepsin B (CTSB) substrate, ProSense 680, is evaluated in the dystrophin deficient mdx mice, a genetic homologue of Duchenne muscular dystrophy via optical imaging.

Results

We show high levels of infrared signal in dystrophic muscle relative to healthy muscle at 24 h post-injection. Imaging for CTSB presence revealed localization to inflammatory infiltrates and regenerating muscle fibers. A time series myotoxin-induced muscle injury experiment showed that CTSB activity and its mRNA levels peaked at the interface between inflammation and myoblast fusion stage of recovery. Prednisone treatment in mdx mice resulted in decreased CTSB activity and increased grip strength in forelimbs and hindlimbs.

Conclusions

Optical imaging of CTSB activity is an ideal method to sensitively monitor inflammation, regeneration, and response to therapy in myopathic skeletal muscle.

Statement of Significance:

Currently, no optical-imaging technique exists for surveying disease pathology of muscle in mouse models of myopathy. Optical imaging offers high sensitivity of probe detection and ease of use, making it an ideal method for monitoring muscle pathology and response to therapy in a dystrophic mdx mouse model. We determined that ProSense 680, a caged near-infrared substrate for cathepsin B, was ideal for relaying the status of both regeneration and inflammatory infiltration in skeletal muscle. Prosense 680 was highly effective at optically distinguishing inflammation in bl10 and mdx forelimb and hindlimb skeletal muscle, and was effective at tracking damage in a myotoxin-induced model of muscle injury.