Christiansen S P, Sandnas A, Prill R, Youle R J, McLoon L K
Department of Ophthalmology, University of Minnesota, Minneapolis 55455, USA.
Invest Ophthalmol Vis Sci. 2000 Oct;41(11):3402-9.
To determine the acute histologic and ultrastructural effects of a recently developed muscle-specific immunotoxin, ricin-mAb 35.
Graduated doses of ricin-mAb 35, composed of ricin conjugated to a monoclonal antibody against the nicotinic acetylcholine receptor of skeletal muscle, were injected into one superior rectus muscle in rabbits. After 3, 7, and 14 days, both superior rectus muscles were removed and prepared for electron microscopy and histologic examination, by using a number of immunohistochemical markers to identify inflammatory cell infiltration, muscle fiber loss, and muscle regeneration.
Myotoxicity of the ricin-mAb 35 was focal and dose related. At the highest dose tested, there was substantial inflammatory cell infiltrate by 3 days, which largely disappeared by 7 days. Significant muscle loss was apparent by 7 days after ricin-mAb 35 treatment. Both the inflammatory reaction and muscle fiber loss were confined to the immediate injection site. Surrounding muscle appeared to be normal. At 14 days after treatment, early signs of muscle regeneration were evident within the tissue sections. No evidence of orbital or systemic toxicity was seen in any animal.
Direct injection of ricin-mAb 35 into the extraocular muscles of rabbits results in a dose-related focal injury to the muscles, with a self-limited inflammatory component and significant muscle fiber loss. This novel immunotoxin may be useful in the treatment of strabismus if chronic studies show a sustained histologic and electrophysiologic effect.
确定一种新开发的肌肉特异性免疫毒素蓖麻毒素 - 单克隆抗体35（ricin - mAb 35）的急性组织学和超微结构效应。
将由与抗骨骼肌烟碱型乙酰胆碱受体单克隆抗体偶联的蓖麻毒素组成的不同剂量的ricin - mAb 35注入兔的一条上直肌。在3天、7天和14天后，取出双侧上直肌，通过使用多种免疫组织化学标记物来识别炎症细胞浸润、肌纤维损失和肌肉再生，制备用于电子显微镜检查和组织学检查的样本。
ricin - mAb 35的肌毒性是局灶性的且与剂量相关。在测试的最高剂量下，3天时出现大量炎症细胞浸润，到7天时基本消失。ricin - mAb 35治疗7天后明显出现显著的肌肉损失。炎症反应和肌纤维损失均局限于直接注射部位。周围肌肉似乎正常。治疗14天后，组织切片内可见肌肉再生的早期迹象。在任何动物中均未观察到眼眶或全身毒性的证据。
将ricin - mAb 35直接注射到兔眼外肌中会导致与剂量相关的肌肉局灶性损伤，伴有自限性炎症成分和显著的肌纤维损失。如果长期研究显示出持续的组织学和电生理效应，这种新型免疫毒素可能对斜视治疗有用。
