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 μg/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/cm3 compared with 27.7 mN/cm3 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.
Bibliographical noteFunding Information:
All experimental procedures were reviewed and preapproved by the Institutional Animal Care and Use Committee at the University of Minnesota, and conform to published guidelines of the National Institutes of Health (NIH) for use of animals in research. Adult New Zealand white rabbits were obtained from Birchwood Farms (Red Wing, Minn) and housed with Research Animal Resources at the University of Minnesota.