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Extraocular muscle force generation after ricin-mAb35 injection: implications for strabismus treatment
Stephen P Christiansen1, Bryan A Becker, Paul A Iaizzo
1Department of Ophthalmology, University of Minnesota, Minneapolis 55455, USA.
Purpose:
Ricin-mAb35 is an immunotoxin targeted against skeletal muscle. Previously, we have shown that injection of ricin-mAb35 into rabbit extraocular muscle results in long-term muscle loss, and we have proposed this as a potential treatment for strabismus. In this study, we assessed the effects of ricin-mAb35 injection on extraocular muscle force generation.
Methods:
Ricin-mAb35, 0.2 microg/kg in a volume of 0.1 mL, was injected into 1 superior rectus muscle in 16 adult rabbits. The contralateral superior rectus was injected with an equal volume of normal saline. Muscle force generation was assessed in vivo at 1, 6, and 12 weeks. Isometric length-tension curves were developed. Single-twitch tension, peak tetanic force generation, and fatigue rate were determined at optimal preload. Data from treated and control muscles were compared with the paired t test.
Results:
Force generation declined in ricin-mAb35 treated muscles at each postinjection interval. At 12 weeks, mean tetanic tension (200 Hz) in treated muscles was 13.8 mN/cm(3) compared with 27.7 mN/cm(3) in saline-injected controls (P =.02), a reduction of 50%. Single-twitch tension at 12 weeks was reduced 33% compared to controls (P =.04). Similar effects were noted at 1 and 6 weeks. Fatigue rate was not greater in treated muscles at any postinjection intervals.
Conclusions:
Injection of ricin-mAb35 results in sustained weakness in extraocular muscle, although additional studies will be required to determine the duration of physiologic effect. These results confirm our histological analysis and suggest that ricin-mAb35 may be a more long-term alternative to botulinum toxin A for the treatment of strabismus.
Insights
Ricin-mAb35 immunotoxin injection significantly reduced extraocular muscle force generation in rabbits, indicating sustained muscle weakness. This finding supports its potential as a long-term strabismus treatment alternative.
Area of Science:
- Ophthalmology
- Muscle Physiology
- Immunotoxicology
Background:
- Ricin-mAb35 is an immunotoxin targeting skeletal muscle.
- Previous studies demonstrated long-term muscle loss in rabbit extraocular muscles after ricin-mAb35 injection.
- This immunotoxin has been proposed as a potential therapeutic agent for strabismus.
Purpose of the Study:
- To evaluate the impact of ricin-mAb35 injection on extraocular muscle force generation.
- To assess the functional changes in muscle strength following targeted immunotoxin administration.
- To provide further evidence for the potential of ricin-mAb35 in strabismus treatment.
Main Methods:
- Adult rabbits received injections of ricin-mAb35 (0.2 microg/kg) into one superior rectus muscle, with the contralateral muscle receiving saline as a control.
- In vivo muscle force generation was measured at 1, 6, and 12 weeks post-injection.
- Isometric length-tension curves, single-twitch tension, peak tetanic force, and fatigue rates were determined.
Main Results:
- Ricin-mAb35 treated muscles exhibited significantly reduced force generation at all measured intervals.
- At 12 weeks, mean tetanic tension was reduced by 50% (13.8 mN/cm(3) vs. 27.7 mN/cm(3), P=.02).
- Single-twitch tension decreased by 33% (P=.04) at 12 weeks; fatigue rates were not significantly altered.
Conclusions:
- Ricin-mAb35 injection induces sustained weakness in extraocular muscles.
- These functional results corroborate histological findings and support ricin-mAb35 as a potential long-term alternative to botulinum toxin A for strabismus.
- Further studies are needed to ascertain the full duration of the observed physiological effects.
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