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SP Christiansen, BA Becker, LK McLoon; Decreased Muscle Strength in Extraocular Muscle Treated with Ricin-mAb35: Implications for Strabismus Treatment . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1463.
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Purpose: Ricin-mAb35 is an immunotoxin targeted against mature myofibers in skeletal muscle. In previous studies, we have shown that direct injection of ricin-mAb35 into rabbit extraocular muscle results in discrete, titratable, long-term muscle loss, and have proposed this as a potential new pharmacological treatment for strabismus. In this study, we assessed the effects of ricin-mAb35 injection on extraocular muscle force generation to determine if treated muscles show sustained weakness, reflecting changes in muscle morphometry. Methods: Ricin-mAb35, 0.2µg/kg in a volume of 0.1cc, was injected into one superior rectus muscle in adult NZW rabbits. The contralateral superior rectus was injected with an equal volume of normal saline. Muscle force generation was assessed in vivo in anesthetized animals at 1, 6 and 12 weeks. Both treated and control superior rectus muscles were disinserted and attached to force transducers. A supramaximal stimulus (0.1 Hz, 0.4 msec) was delivered to the muscles via platinum bipolar contact electrodes, and isometric length-tension curves were developed. Single-twitch tension, peak tetanic force generation, and fatigue rate were then determined at optimal pre-load. Data from treated and control muscles were pooled at each post-injection interval and compared with the Student's t-test. Results: Both single-twitch and tetanic force generation were reduced in ricin-mAb35 treated muscles at each post-injection interval. At 6 weeks, mean developed tetanic tension (200 Hz) in treated muscles was 10.4 mN/cm3 compared with 26.7 mN/cm3 in saline-treated controls (p<0.05). Single-twitch tension at six weeks was reduced 57% in treated muscles compared to controls. Similar effects were noted at 12 weeks. Fatigue rate was not altered by ricin treatment of muscles even at 1 week. Conclusion: These findings demonstrate that injection of ricin-mAb35 results in sustained weakness in extraocular muscle. 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.
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