Myotoxic effects of the skeletal muscle-specific immunotoxin, ricin-mAb35, on orbicularis oculi muscle after eyelid injections in rabbits.

Abstract

The authors recently demonstrated that a single injection of the immunotoxin ricin-mAb35 has potent and long-lasting myotoxic effects in extraocular muscles. The myotoxicity of injected ricin-mAb35 was tested in the eyelids of rabbits to determine its potential for use in the treatment of benign essential blepharospasm and other dystonias. The immunotoxin ricin-mAb35 was injected in one eyelid of adult rabbits. After 1 week, 1 month, or 6 months, the rabbits were euthanized, and the eyelids were prepared for histologic examination of inflammatory cell infiltrate with immunohistochemical localization of cd11b and myosin heavy chain isoform expression. Muscle loss was quantified by analysis of muscle fiber cross-sectional area and total myofiber number. Within the first week after a single injection of ricin-mAb35, some edema developed, which resolved by the second week. Otherwise, the eyelids were normal in appearance. A short-lived inflammatory response was seen at 1 week, but this resolved 1 month after treatment. One week after injection, there was a significant decrease in the total number of orbicularis oculi myofibers in the ricin-mAb35-treated eyelids. This myofiber loss remained significant 1 month later and was maintained 6 months after the initial injection. Direct injection of the immunotoxin ricin-mAb35 resulted in significant, acute muscle loss in the orbicularis oculi of rabbits that was maintained for up to 6 months. Physiologic studies are needed to demonstrate concomitant loss of muscle strength, but these results suggest that ricin-mAb35 injection holds promise as a muscle-weakening agent in the eyelid.