McLoon L K, Kirsch J D, Cameron S, Wirtschafter J D
Department of Ophthalmology, University of Minnesota, Minneapolis 55455.
Brain Res. 1994 Mar 28;641(1):105-10. doi: 10.1016/0006-8993(94)91821-x.
In both laboratory and clinical studies, injection of doxorubicin directly into the eyelid results in permanent muscle loss of the majority of fibers within treated eyelids. A first clinical trial of this technique in blepharospasm and hemifacial spasm patients has been performed. All patients who completed a full course of doxorubicin treatment showed a permanent decrease in eyelid strength, with over 50% of these patients requiring no further treatment. Doxorubicin is known to be carried by retrograde axonal transport to the brain and is a known neurotoxin. This raises the question of the effect of these treatments on the facial neurons which innervate the orbicularis oculi muscle in the eyelids. The effect on the number of facial neurons present after injection of doxorubicin into the eyelid of rabbits was determined using both HRP and diI retrograde labeling techniques. Despite the extensive and permanent muscle loss caused by the doxorubicin treatments, there was no measurable loss of facial neurons on the doxorubicin treated sides. DiI was shown to be myotoxic at high concentrations and amplified the myotoxic effect of doxorubicin. Lack of neuronal loss may offer assurance of clinical safety to the facial motor neurons of muscle spasm patients who receive doxorubicin injections into their eyelids.
在实验室研究和临床研究中,将阿霉素直接注射到眼睑内会导致治疗眼睑内大多数纤维出现永久性肌肉损失。已对该技术在眼睑痉挛和半面痉挛患者中进行了首次临床试验。所有完成阿霉素全疗程治疗的患者眼睑力量均出现永久性下降,其中超过50%的患者无需进一步治疗。已知阿霉素通过逆行轴突运输至大脑,并且是一种已知的神经毒素。这就提出了这些治疗对支配眼睑眼轮匝肌的面部神经元有何影响的问题。使用HRP和DiI逆行标记技术确定了将阿霉素注射到兔眼睑后对面部神经元数量的影响。尽管阿霉素治疗导致广泛且永久性的肌肉损失,但在接受阿霉素治疗的一侧未检测到面部神经元损失。已证明高浓度的DiI具有肌毒性,并放大了阿霉素的肌毒性作用。神经元未损失可能为接受眼睑注射阿霉素的肌肉痉挛患者的面部运动神经元提供临床安全性保证。