Mitochondrial morphometrics of histochemically identified human extraocular muscle fibers

Abstract

Three fiber types--coarse, granular, and fine--were readily identified in histochemical cryostat sections of human extraocular muscle (EOM). The cryostat retrieval method was utilized to identify these three fiber types in serial electron microscopic thin sections. Using morphometric techniques, five mitochondrial variables (mitochondrial volume fraction, mitochondrial profile size, mitochondrial profile density, and clusters of two or of three or more mitochondrial profiles) were determined for a total of 162 histochemically identified fibers from two regions (orbital and global zones) from six EOMs. Coarse fibers had numerous large-sized mitochondrial profiles, often occurring in clusters. Granular fibers had fewer and smaller-sized profiles scattered across the fiber. Fine fibers had the most numerous, but smallest-sized mitochondrial profiles. Despite significant differences in group (fiber types) means for the mitochondrial variables, no single variable was sufficient for separating fiber types into distinct populations. Although a scattergram plot of two variables was sufficient to separate orbital zone fibers, a computer-generated, multivariate discriminant analysis was needed to separate the global zone fibers into distinct populations. These results will aid future studies on normal and pathological human EOM by providing a morphometric basis for identifying fiber types in the orbital and global zones.

Somatic Mitochondrial DNA Deletions Accumulate to High Levels in Aging Human Extraocular Muscles

“…40 As a consequence, EOM and skeletal muscle fibers exhibit fundamental differences in their fiber type composition, their myosin heavy chain isoform expression, and the basic organization of their motor units. 41,42 Of importance, because of the need for sustained muscular contractions and fatigue resistance, 43 EOMs have a higher mitochondrial content than do skeletal muscles, 44 and they possess a richer vascular supply to support these greater metabolic requirements. 45 It is also important to note that a population of activated satellite cells has been identified in normal EOMs, resulting in a slow but continuous myonuclear addition to existing myofibers, The variants listed were not found in other single EOM fibers sequenced from the same patient, and the following databases were checked to determine whether these had been reported as mtDNA single nucleotide polymorphisms: MITOMAP 29 unlike skeletal muscle where satellite cells remain quiescent in the noninjured state.…”

Mitochondrial myopathies and encephalomyopathies

“…Only 50% of patients with a progressive extraocular myopathy have deletions of mtDNA [7], but in contrast CPEO is a universal feature of patients with mtDNA deletions in muscle. It is noteworthy in this context that the mitochondrial volume fraction in extraocular muscles is 3-4 times greater than in limb muscles which may explain their particular susceptibility [8].…”

“…Typically these patients have involvement of extraocular muscles, including ptosis, and later a symptomatic proximal myopathy. It is noteworthy in this context that the mitochondrial volume fraction in extraocular muscles is 3-4 times greater than in limb muscles which may explain their particular susceptibility [8]. Some may also have a pigmentary retinopathy or evidence of CNS disease, but in general this is a fairly mild mitochondrial disease.…”

Structure, innervation, and age‐associated changes of mouse forearm muscles

“…The proliferation of mitochondria in the fibers of these patients ,404 (195) may be related to the overall decreased levels of respiratory chain enzymes in the muscles. The extraocular muscle fibers may be more susceptible to the formation of ragged-red fibers than other fibers due to their normally high concentrations of mitochondria (Carry et al, 1986). The mouse forearm muscle fibers, particularly the SO and FOG fibers, with their high intense staining characteristics for oxidative enzymes, and thus numerous mitochondria, may likewise be more susceptible to age-associated defects in mitochondrial function.…”