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S.P. Christiansen, B.A. Becker, L.K. McLoon; Long-term Effects of Ricin-mAb35 Injection on Extraocular Muscle Force Generation in Rabbits . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3124.
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Purpose: Ricin-mAb35 is an immunotoxin targeted to skeletal muscle that may hold promise for the treatment of strabismus. When injected in extraocular muscle (eom), it creates a discrete injury pattern, followed by slow regenerative growth and recovery within one year. In physiologic studies, we have shown a 50 percent decrease in generated tension that persists through 3 months. The purpose of this study is to determine the longer-term effects of ricin-mAb35 injection on eom force generation. Methods: In 16 NZW rabbits, ricin-mAb35, 0.2µg/kg in a volume of 0.1ml, was injected into one superior rectus muscle. The contralateral superior rectus muscle was injected with 0.1ml of normal saline. At post-injection intervals of 24 and 48 weeks, in vivo physiologic testing of both superior rectus muscles was performed. After determining supra-threshold stimulus intensities and optimal pre-load for each muscle, single twitch tension, generated tension at increasing stimulus frequency, and fatigability were tested. At the completion of testing, both superior rectus muscles were removed for histological examination. Pooled data for both treatment and control muscles at each post-injection interval were compared with the paired t-test. Results: At 24 weeks, generated tension in treated eom ranged between 70 and 81 percent of saline-treated controls at stimulation frequencies ranging between 10 and 200 Hz. Single-twitch tension in treated eom was 78 percent of control. Treated muscle was no more fatigable than control eom. By 48 weeks, there was no statistically significant difference in treated and control muscles for any of the parameters tested. Conclusions: In strabismus, the optimal duration of treatment effect for ricin-mAb35 and other pharmacological agents under development is unknown. Certainly, permanent eom weakness is not desired as it could predispose to late overcorrection. The results of this study indicate that recovery of eom strength following ricin-mAb35 is complete by 1 year post-injection. Future studies will be required to test the effectiveness of this agent in the treatment of strabismus.
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