Christiansen Stephen P, Becker Bryan A, Iaizzo Paul A, McLoon Linda K
Department of Ophthalmology, University of Minnesota, Minneapolis 55455, USA.
J AAPOS. 2003 Feb;7(1):1-6. doi: 10.1067/mpa.2003.S1091853103000569.
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.
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.
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.
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.
蓖麻毒素 - mAb35是一种靶向骨骼肌的免疫毒素。此前，我们已经表明，将蓖麻毒素 - mAb35注射到兔眼外肌中会导致长期的肌肉损失，并且我们已提出这可作为斜视的一种潜在治疗方法。在本研究中，我们评估了注射蓖麻毒素 - mAb35对眼外肌力量产生的影响。
将0.2微克/千克、体积为0.1毫升的蓖麻毒素 - mAb35注射到16只成年兔的1条上直肌中。对侧上直肌注射等体积的生理盐水。在第1、6和12周时在体内评估肌肉力量产生情况。绘制等长长度 - 张力曲线。在最佳预负荷下测定单收缩张力、强直收缩峰值力量和疲劳率。将处理组和对照组肌肉的数据进行配对t检验。
在每个注射后时间间隔，蓖麻毒素 - mAb35处理的肌肉力量产生均下降。在12周时，处理组肌肉的平均强直张力（200赫兹）为13.8毫牛/平方厘米，而注射生理盐水的对照组为27.毫牛/平方厘米（P = 0.02），降低了50%。与对照组相比，12周时单收缩张力降低了33%（P = 0.04）。在第1周和第6周时也观察到类似效果。在任何注射后时间间隔，处理组肌肉的疲劳率均未更高。
注射蓖麻毒素 - mAb35会导致眼外肌持续无力，但需要进一步研究来确定生理效应的持续时间。这些结果证实了我们的组织学分析，并表明蓖麻毒素 - mAb35可能是一种比肉毒杆菌毒素A更长期的斜视治疗替代方法。
