Long-term changes in myosin heavy chain composition after botulinum toxin a injection into rat medial rectus muscle.
OBJECTIVE
To study long-term changes of extraocular muscles after botulinum toxin (Botx) A-induced paralysis, with special emphasis on myosin heavy chain (MyHC) isoform pattern in muscle fibers.


METHODS
Botx A (5 IU) was injected into the ocular medial rectus (MR) muscles of adult rats. After 1, 5, and 8 months muscle cross sections were examined immunohistochemically, histochemically, and morphometrically. MyHC content was analyzed by gel electrophoresis.


RESULTS
Paralyzed MR muscles displayed mildly atrophic and hypertrophic muscle fibers and decreased oxidative metabolism, due to decreased succinate dehydrogenase activity. However, muscle morphology was not grossly disturbed. MyHC profile was shifted toward slower isoforms. Electrophoretic analysis showed that the share of MyHCI, and especially of MyHCIIa and MyHCIIx/d, increased several fold, whereas the share of MyHCIIb decreased heavily during the first 5 months. Immunohistochemical analysis generally mirrored the results obtained by electrophoresis. Moreover, specific extraocular MyHC isoform MyHCeom disappeared and could not be detected during the whole experimental period. The portion of MyHCIIb relatively increased 8 months after Botx A injection, although the MyHC profile was still far from normal.


CONCLUSIONS
These long-lasting changes in Botx A-paralyzed ocular MR muscles most probably reflect their inability to regain their unique functional characteristics after new motor end plate formation and recovery of muscle contraction.
Kranjc
B S
BS
University Eye Hospital, Zaloska 29 A, 1000 Ljubljana, Slovenia. branka.stirn@guest.arnes.si
Sketelj
J
J
D'Albis
A
A
Erzen
I
I
D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006651:Histocytochemistry; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D018995:Myosin Heavy Chains / Q000737:chemistry*; D009465:Neuromuscular Agents / Q000494:pharmacology*; D009801:Oculomotor Muscles / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D009886:Ophthalmoplegia / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013997:Time Factors
D009465:Neuromuscular Agents; D013385:Succinate Dehydrogenase; D019274:Botulinum Toxins, Type A; D018995:Myosin Heavy Chains