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Stephen P. Christiansen, Amy Sandnas, Robert Prill, Richard J. Youle, Linda K. McLoon; Acute Effects of the Skeletal Muscle-Specific Immunotoxin Ricin-mAb 35 on Extraocular Muscles of Rabbits. Invest. Ophthalmol. Vis. Sci. 2000;41(11):3402-3409.
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purpose. To determine the acute histologic and ultrastructural effects of a
recently developed muscle-specific immunotoxin, ricin-mAb 35.
methods. 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
results. 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.
conclusions. 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
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