Human Extraocular Muscles in ALS

Abstract

PURPOSE. To investigate the general morphology, fiber type content, and myosin heavy chain (MyHC) composition of extraocular muscles (EOMs) from postmortem donors with amyotrophic lateral sclerosis (ALS) and to evaluate whether EOMs are affected or truly spared in this disease. METHODS. EOM and limb muscle samples obtained at autopsy from ALS donors and EOM samples from four control donors were processed for immunohistochemistry with monoclonal antibodies against distinct MyHC isoforms and analyzed by SDS-PAGE. In addition, hematoxylin and eosin staining and nicotinamide tetrazolium reductase (NADH-TR) activity were studied. RESULTS. Wide heterogeneity was observed in the appearance of the different EOMs from each single donor and between donors, irrespective of ALS type or onset. Pathologic morphologic findings in ALS EOMs included presence of atrophic and hypertrophic fibers, either clustered in groups or scattered; increased amounts of connective tissue; and areas of fatty replacement. The population of fibers stained with anti-MyHCslow tonic was smaller than that of MyHCIpositive fibers and was mostly located in the orbital layer in most of the ALS EOM samples, whereas an identical staining pattern for both fiber populations was observed in the control specimens. MyHCembryonic was notably absent from the ALS EOMs. CONCLUSIONS. The EOMs showed signs of involvement with altered fiber type composition, contractile protein content, and cellular architecture. However, when compared to the limb muscles, the EOMs were remarkably preserved. EOMs are a useful model for the study of the pathophysiology of ALS.

Different Impact of ALS on Laminin Isoforms in Human Extraocular Muscles versus Limb Muscles

“…14 We have previously observed areas of fatty replacement in donor 1/RS; grouped hypertrophic fibers, scattered atrophic fibers, and areas filled with nerve trunks in donor 3/RS; and presence of fibrosis and central nuclei in donor 4/RL. In addition, different EOMs from the same donor showed different levels of involvement in the disease.…”

“…In general, the BM of muscle fibers in the orbital layer displayed higher immunoreactivity than those in the global layer in 10 ALS samples ( Fig. 1A5; Table 3), whereas there 14 the newly added and earliest donor was named Da. The middle part of each EOM listed was examined.…”

“…[7][8][9][10][11][12][13] We recently showed that the extraocular muscles (EOMs) of terminal ALS donors show signs of disease involvement, with the presence of hypertrophic and atrophic muscle fibers, increased connective tissue, as well as changes in myosin heavy chain composition. 14 These pathologic changes were present in both FALS and SALS cases, irrespective of whether they had a bulbar or spinal disease onset. 14 Remarkably, although the EOMs are not completely spared in ALS, they are by far less affected than the spinal-innervated muscles from the same donors.…”

“…14 These pathologic changes were present in both FALS and SALS cases, irrespective of whether they had a bulbar or spinal disease onset. 14 Remarkably, although the EOMs are not completely spared in ALS, they are by far less affected than the spinal-innervated muscles from the same donors.…”

Dystrophic Changes in Extraocular Muscles after Gamma Irradiation in mdx:utrophin+/− Mice

“…After treatment of the EOM with botulinum toxin, the myofibers actually became larger in mean cross-sectional area [22], [52]. In addition to their sparing in DMD, the EOM are also spared in the sarcopenia associated with aging and in neurogenic wasting diseases such as amyotrophic lateral sclerosis [53], [54]. What is not seen in the EOM of humans or animals with these diseases or after injury is the appearance of central nucleation.…”