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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Harrison
Andrew R
AR
Department of Ophthalmology, University of Minnesota, Room 374 Lions Research Building, 2001 6th Street SE, Minneapolis, MN 55455, U.S.A. mcloo001@tc.umn.edu
Skladzien
Stephanie
S
Christiansen
Stephen P
SP
McLoon
Linda K
LK
D000818:Animals; D000911:Antibodies, Monoclonal; D001764:Blepharospasm / Q000188:drug therapy; D039481:CD11b Antigen / Q000378:metabolism; D005143:Eyelids / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007124:Immunoenzyme Techniques; D000922:Immunotoxins / Q000494:pharmacology*; D007267:Injections; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D009801:Oculomotor Muscles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020033:Protein Isoforms / Q000378:metabolism; D011817:Rabbits; D011978:Receptors, Nicotinic / Q000276:immunology; D012276:Ricin / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D039481:CD11b Antigen; D000922:Immunotoxins; D020033:Protein Isoforms; D011978:Receptors, Nicotinic; D012276:Ricin; D018995:Myosin Heavy Chains