Ultrastructural analysis of extraocular muscle in chronic progressive external ophthalmoplegia

Extraocular muscles are primarily involved in many mitochondrial diseases, but no reports exist regarding the morphological appearance of the muscles in cases of long-standing ocular myopathies. For this reason, muscle samples obtained from surgery in a sporadic case of chronic progressive external ophthalmoplegia (CPEO) were used for ultrastructural investigation and molecular analysis of mitochondrial DNA. Genetic testing revealed a heteroplasmic macrodeletion of about 5.0 kilobases in length, localized between the 9570- and 14619-base pair regions. Electron microscopy revealed focal areas of both disruption and abnormality of mitochondria in only some of the muscle fibers, producing "selective vacuolization." This ultrastructural pattern was highly selective and limited to some extraocular muscle fibers, sparing all the others. The "selective damage" observed in this case of CPEO resembles that case occurring in another mitochondrial disease, Leber hereditary optic neuropathy, where damage occurs only in the papillomacular bundle of the retina, sparing peripheral axons. It is possible that some anatomical and physiological factors play a leading role in both Leber hereditary optic neuropathy and ocular myopathies. The ultrastructural aspect herein observed needs to be further investigated to better understand whether a particular muscle fiber type is the target of mitochondrial impairment in CPEO.