A Novel Type of Multiterminal Motor Endplate in Human Extraocular Muscles

Liu, Jing‐Xia; Domellöf, Fátima Pedrosa

doi:10.1167/iovs.17-22554

Cited by 11 publications

(26 citation statements)

References 27 publications

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“…In addition, sporadic myofibers containing MyHCeom or MyHCsto/I displayed clustered small "grape-like" endplates on either side of the muscle fiber, as described previously. 15 Desmin was always detected in these myofibers irrespective of myofiber type and location (not shown).…”

Section: Desmin In Myhceom Myofibers With Multiterminal En Plaque Andmentioning

confidence: 82%

“…Subsequently, immunolabeling for the third or fourth primary antibody against desmin or MyHCs was performed, followed by incubation with the appropriate secondary antibody for 30 minutes at 37°C, as previously described. 15 Control sections were treated as previously mentioned, except that the primary antibodies were omitted. No staining was observed in control sections.…”

Section: Immunofluorescencementioning

confidence: 99%

“…Three types of muscle fibers were classified in the human EOMs on the basis of their MyHC isoform content, as previously described. 10,15 In brief, the muscle fibers strongly labeled with the antibody against MyHCsto and in the vast majority, also strongly labeled with the antibody against MyHCI, were classified as muscle fibers containing MyHCsto/I. The myofibers strongly or moderately labeled with the antibody against MyHCIIa were classified as muscle fibers containing MyHCIIa.…”

Section: Myofiber Typing In Human Eomsmentioning

confidence: 99%

“…23,24 We very recently reported a novel type of large multiterminal en plaque motor endplates which are abundant and exclusively present in myofibers containing MyHCeom in the human EOMs. 15 Some of these myofibers may in fact be polyinnervated, as adjacent endplates show different acetylcholine receptor (AChR) subunits. 15 Because of this novel type of multiterminal innervation, we try not to use the terms MIFs and SIFs to avoid misinterpretation of the data related to the myofibers containing MyHCsto/I and the myofibers containing MyHCeom.…”

mentioning

confidence: 99%

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Complex Correlations Between Desmin Content, Myofiber Types, and Innervation Patterns in the Human Extraocular Muscles

Liu

Domellöf

2020

Invest. Ophthalmol. Vis. Sci.

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Citation: Liu J-X, Pedrosa Domellöf F. Complex correlations between desmin content, myofiber types, and innervation patterns in the human extraocular muscles. Invest Ophthalmol Vis Sci. 2020;61(3):15. https://doi.org/10.1167/iovs.61.3.15 PURPOSE. To investigate whether the distribution of intermediate filament protein desmin is related to the different patterns of innervation in the human extraocular muscles (EOMs).METHODS. EOM samples were analyzed with immunohistochemistry using antibodies against desmin, vimentin, different myosin heavy chain (MyHC) isoforms, and fetal and adult acetylcholine receptor (AChR) subunits. Neuromuscular junctions (NMJs) were identified with α-bungarotoxin or with antibodies against neurofilament and synaptophysin. RESULTS.Desmin was present in the vast majority of myofibers, but it was weakly present or absent in a limited area in the close vicinity of the single en plaque NMJs in less than half of these myofibers. Desmin was either present or lacking in MyHCsto/I myofibers displaying multiple en grappe endings but present in MyHCsto/I myofibers receiving spiral nerve endings. In MyHCeom myofibers displaying multiterminal en plaque endings, desmin was either present or absent irrespective of AChR subunits or EOM layer. Vimentin did not substitute for the lack of desmin. CONCLUSIONS.The results indicate that the human EOMs have a more complex cytoskeletal organization than other muscles and suggest additional signalling mechanisms from the NMJs to the myofibers.

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Section: Desmin In Myhceom Myofibers With Multiterminal En Plaque Andmentioning

confidence: 82%

Section: Immunofluorescencementioning

confidence: 99%

Section: Myofiber Typing In Human Eomsmentioning

confidence: 99%

mentioning

confidence: 99%

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Complex Correlations Between Desmin Content, Myofiber Types, and Innervation Patterns in the Human Extraocular Muscles

Liu

Domellöf

2020

Invest. Ophthalmol. Vis. Sci.

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“…The remaining 15-20% of the EOM nerve fibers are small and innervate many small, "en grappe" motor endplates along the length of a muscle fiber (the so-called multiply innervated muscle fibers, reviewed in [11]). This traditional description of the innervation of the EOMs has been significantly changed by the recent report of a subpopulation of muscle fibers that exhibit multiple large "en plaque" nerve endings [14]. The NMJs of the EOMs also differ from limb muscle in retaining expression of the fetal gamma subunit of the acetylcholine receptor (AChR), in addition to the adult epsilon subunit, typically present in mature motor endplates [14,15].…”

Section: Introductionmentioning

confidence: 99%

The Extraocular Muscles Are Selectively Spared in ALS

Domellöf¹

2020

Amyotrophic Lateral Sclerosis - Recent Advances and Therapeutic Challenges

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The extraocular muscles differ from other skeletal muscles in many respects but most strikingly in their response to neuromuscular diseases expected to affect the whole body. Oculomotor disturbances are not typical features of ALS. Recent data ascribe the muscle tissue an important role in the pathophysiology of ALS, with early involvement of the neuromuscular junctions and loss of axonal contact. We show that the extraocular muscles of terminal ALS donors and also of mice models of ALS maintain their morphology and well-preserved neuromuscular junctions until the end stages of the disease, whereas the limb muscles are severely affected and their neuromuscular junctions start losing contact with the supplying axons early in the course of ALS. There are intrinsic differences between the extraocular and limb muscles with respect to neurotrophic factors and Wnt isoforms and fundamental differences in their response to ALS that cannot be explained by the aging process. We propose that these differences may be instrumental in the selective sparing of the extraocular muscles in ALS.

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Clinical and imaging clues to the diagnosis and follow‐up of ptosis and ophthalmoparesis

Keene

Kan

Meeren

et al. 2022

J cachexia sarcopenia muscle

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Ophthalmoparesis and ptosis can be caused by a wide range of rare or more prevalent diseases, several of which can be successfully treated. In this review, we provide clues to aid in the diagnosis of these diseases, based on the clinical symptoms, the involvement pattern and imaging features of extra‐ocular muscles (EOM). Dysfunction of EOM including the levator palpebrae can be due to muscle weakness, anatomical restrictions or pathology affecting the innervation. A comprehensive literature review was performed to find clinical and imaging clues for the diagnosis and follow‐up of ptosis and ophthalmoparesis. We used five patterns as a framework for differential diagnostic reasoning and for pattern recognition in symptomatology, EOM involvement and imaging results of individual patients. The five patterns were characterized by the presence of combination of ptosis, ophthalmoparesis, diplopia, pain, proptosis, nystagmus, extra‐orbital symptoms, symmetry or fluctuations in symptoms. Each pattern was linked to anatomical locations and either hereditary or acquired diseases. Hereditary muscle diseases often lead to ophthalmoparesis without diplopia as a predominant feature, while in acquired eye muscle diseases ophthalmoparesis is often asymmetrical and can be accompanied by proptosis and pain. Fluctuation is a hallmark of an acquired synaptic disease like myasthenia gravis. Nystagmus is indicative of a central nervous system lesion. Second, specific EOM involvement patterns can also provide valuable diagnostic clues. In hereditary muscle diseases like chronic progressive external ophthalmoplegia (CPEO) and oculo‐pharyngeal muscular dystrophy (OPMD) the superior rectus is often involved. In neuropathic disease, the pattern of involvement of the EOM can be linked to specific cranial nerves. In myasthenia gravis this pattern is variable within patients over time. Lastly, orbital imaging can aid in the diagnosis. Fat replacement of the EOM is commonly observed in hereditary myopathic diseases, such as CPEO. In contrast, inflammation and volume increases are often observed in acquired muscle diseases such as Graves' orbitopathy. In diseases with ophthalmoparesis and ptosis specific patterns of clinical symptoms, the EOM involvement pattern and orbital imaging provide valuable information for diagnosis and could prove valuable in the follow‐up of disease progression and the understanding of disease pathophysiology.

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A Novel Type of Multiterminal Motor Endplate in Human Extraocular Muscles

Cited by 11 publications

References 27 publications

Complex Correlations Between Desmin Content, Myofiber Types, and Innervation Patterns in the Human Extraocular Muscles

Complex Correlations Between Desmin Content, Myofiber Types, and Innervation Patterns in the Human Extraocular Muscles

The Extraocular Muscles Are Selectively Spared in ALS

Clinical and imaging clues to the diagnosis and follow‐up of ptosis and ophthalmoparesis

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