Myosin Heavy Chain Expression in Mouse Extraocular Muscle: More Complex Than Expected

Zhou, Yuefang; Liú, Dan; Kaminski, Henry J.

doi:10.1167/iovs.10-5937

Cited by 50 publications

(79 citation statements)

References 21 publications

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“…51 Variability in expression levels of IGF1 in strabismic muscles likely reflects variability in causes and/or phases of strabismus, 12 or a mismatch between gene expression and protein levels. 31,52 …”

Section: Discussionmentioning

confidence: 99%

Altered Protein Composition and Gene Expression in Strabismic Human Extraocular Muscles and Tendons

Agarwal

Feng

Altick

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PurposeTo determine whether structural protein composition and expression of key regulatory genes are altered in strabismic human extraocular muscles.MethodsSamples from strabismic horizontal extraocular muscles were obtained during strabismus surgery and compared with normal muscles from organ donors. We used proteomics, standard and customized PCR arrays, and microarrays to identify changes in major structural proteins and changes in gene expression. We focused on muscle and connective tissue and its control by enzymes, growth factors, and cytokines.ResultsStrabismic muscles showed downregulation of myosins, tropomyosins, troponins, and titin. Expression of collagens and regulators of collagen synthesis and degradation, the collagenase matrix metalloproteinase (MMP)2 and its inhibitors, tissue inhibitor of metalloproteinase (TIMP)1 and TIMP2, was upregulated, along with tumor necrosis factor (TNF), TNF receptors, and connective tissue growth factor (CTGF), as well as proteoglycans. Growth factors controlling extracellular matrix (ECM) were also upregulated. Among 410 signaling genes examined by PCR arrays, molecules with downregulation in the strabismic phenotype included GDNF, NRG1, and PAX7; CTGF, CXCR4, NPY1R, TNF, NTRK1, and NTRK2 were upregulated. Signaling molecules known to control extraocular muscle plasticity were predominantly expressed in the tendon rather than the muscle component. The two horizontal muscles, medial and lateral rectus, displayed similar changes in protein and gene expression, and no obvious effect of age.ConclusionsQuantification of proteins and gene expression showed significant differences in the composition of extraocular muscles of strabismic patients with respect to important motor proteins, elements of the ECM, and connective tissue. Therefore, our study supports the emerging view that the molecular composition of strabismic muscles is substantially altered.

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Section: Discussionmentioning

confidence: 99%

Altered Protein Composition and Gene Expression in Strabismic Human Extraocular Muscles and Tendons

Agarwal

Feng

Altick

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…Although the unique anatomical and physiological features of EOMs have drawn much interest (Andrade et al, 2000; da Silva Costa et al, 2012; Spencer and Porter, 2006; Zhou et al, 2010), knowledge about the EOM myogenic progenitors is currently limited. One study that has used transgenic Pax7-nGFP mice for isolating and characterizing myogenic progenitors, placed the Pax7 + SCs as the main myogenic population in adult EOM as in the other muscles (Sambasivan et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Extraocular muscle satellite cells are high performance myo-engines retaining efficient regenerative capacity in dystrophin deficiency

Stuelsatz

Shearer

et al. 2015

Developmental Biology

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Extraocular muscles (EOMs) are highly specialized skeletal muscles that originate from the head mesoderm and control eye movements. EOMs are uniquely spared in Duchenne muscular dystrophy and animal models of dystrophin deficiency. Specific traits of myogenic progenitors may be determinants of this preferential sparing, but very little is known about the myogenic cells in this muscle group. While satellite cells (SCs) have long been recognized as the main source of myogenic cells in adult muscle, most of the knowledge about these cells comes from the prototypic limb muscles. In this study, we show that EOMs, regardless of their distinctive Pax3-negative lineage origin, harbor SCs that share a common signature (Pax7+, Ki67−, Nestin-GFP+, Myf5nLacZ+, MyoD-positive lineage origin) with their limb and diaphragm somite-derived counterparts, but are remarkably endowed with a high proliferative potential as revealed in cell culture assays. Specifically, we demonstrate that in adult as well as in aging mice, EOM SCs possess a superior expansion capacity, contributing significantly more proliferating, differentiating and renewal progeny than their limb and diaphragm counterparts. These robust growth and renewal properties are maintained by EOM SCs isolated from dystrophin-null (mdx) mice, while SCs from muscles affected by dystrophin deficiency (i.e., limb and diaphragm) expand poorly in vitro. EOM SCs also retain higher performance in cell transplantation assays in which donor cells were engrafted into host mdx limb muscle. Collectively, our study provides a comprehensive picture of EOM myogenic progenitors, showing that while these cells share common hallmarks with the prototypic SCs in somite-derived muscles, they distinctively feature robust growth and renewal capacities that warrant the title of high performance myo-engines and promote consideration of their properties for developing new approaches in cell-based therapy to combat skeletal muscle wasting.

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“…EOMs are skeletal muscles with unique properties, including patterns of gene expression very different from skeletal muscle and altered susceptibility to systemic myopathies. 1-5 …”

Section: Introductionmentioning

confidence: 99%

Development of Extraocular Muscles Requires Early Signals From Periocular Neural Crest and the Developing Eye

Bohnsack

Gallina

Thompson³

et al. 2011

Arch Ophthalmol

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Myosin Heavy Chain Expression in Mouse Extraocular Muscle: More Complex Than Expected

Cited by 50 publications

References 21 publications

Altered Protein Composition and Gene Expression in Strabismic Human Extraocular Muscles and Tendons

Altered Protein Composition and Gene Expression in Strabismic Human Extraocular Muscles and Tendons

Extraocular muscle satellite cells are high performance myo-engines retaining efficient regenerative capacity in dystrophin deficiency

Development of Extraocular Muscles Requires Early Signals From Periocular Neural Crest and the Developing Eye

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