Apoptotic muscle fiber degeneration in distal myopathy with rimmed vacuoles

Rimmed vacuole formation, tubulofilamentous nuclear inclusions and muscle f iber atrophy are the characteristic pathological findings in distal myopath y with rimmed vacuoles (DMRV). Necrotic muscle fibers were few in number an d did not appear to account for the muscle weakness, but the nuclear change s with myofibrillar degeneration followed by rimmed vacuole formation appea red to be the major reason for the muscle fiber atrophy in DMRV. To determi ne whether the nuclear change in DMRV was related to apoptosis, we examined 15 muscle biopsy specimens immunohistochemically, and 7 of them ultrastruc turally. The characteristic tubulofilamentous nuclear inclusions were found in 4 and the typical fragmented apoptotic nuclei in 3 of the 7 muscle biop sy samples examined by electron microscopy. TUNEL-positive nuclei reflectin g apoptotic DNA fragmentation were found in 13 of 15 biopsies ranging from a few to approximately 1.5% of myonuclei. Apoptosis-specific protein was ex pressed in the sarcoplasm of atrophic fibers in 13 biopsies both with or wi thout rimmed vacuoles. These findings suggest that the apoptotic process pl ays a crucial role in myofibrillar degeneration followed by autophagocytosi s, i.e., rimmed vacuole formation, in DMRV.