Long-term changes in myosin heavy chain composition after botulinum toxin A injection into rat medial rectus muscle

PURPOSE. To study long-term changes Of extraocular muscles after botulinum toxin (Botx) A-induced paralysis, with special emphasis on myosin heavy cha in (MyHC) isoform pattern in muscle fibers. METHODS. Botx A (5 IU) was injected into the ocular medial rectus (MR) musc les of adult rats. After 1, 5, and 8 months Muscle cross sections were exam ined immunohistochemically, histochemically, and morphometrically. MyHC con tent was analyzed by gel electrophoresis. RESULTS. Paralyzed MR muscles displayed mildly atrophic and hypertrophic mu scle fibers and decreased oxidative metabolism, due to decreased succinate dehydrogenase activity. However, muscle morphology was not grossly disturbe d. MyHC profile was shifted toward slower isoforms. Electrophoretic analysi s showed that the share of MyHCl, and especially of MyHCIIa and MyHCIIx/d, increased several fold, whereas the share of MyHCIIb decreased heavily duri ng the first 5 months. Immunohistochemical analysis generally mirrored the results obtained by electrophoresis. Moreover, specific extraocular MyHC is oform MyHCeom disappeared and could not be detected during the whole experi mental period. The portion of MuHCIIb relatively increased 8 months after B otx A injection, although the MyHC profile was still far from normal. CONCLUSIONS. These long-lasting changes in Botx A-paralyzed ocular MR muscl es most probably reflect their Inability to regain their unique functional characteristics after new motor end plate formation and recovery of muscle contraction.