Abnormal expression of seven myogenesis-related genes in extraocular muscles of patients with concomitant strabismus

Abstract

Abstract. Hyperplasia or hypoplasia of muscles gradually leads to strabismus. Myogenesis-related genes are involved in extraocular muscle development, including myogenic differentiation 1 (MYOD1), myogenin (MYOG), retinoblastoma 1 (RB1), cyclin-dependent kinase inhibitor 1A (P21), cyclin-dependent kinase inhibitor 1C (P57), insulin-like growth factor 1 (IGF1) and muscle creatine kinase (MCK). This study evaluated the expression of the above seven myogenesis-related genes by realtime quantitative RT-PCR in 18 resected extrocular muscles of patients with concomitant strabismus and 12 normal control muscle samples from one presumably healthy male 6 h after sudden mortality. We found that although there was a great divergence among the expression levels of 6 myogenesis-related regulatory factors, the relative expression patterns were similar in all the normal muscles, including the synergistic, antagonistic and yoke muscles. However, their expression levels in the 18 diseased extraocular muscles were abnormal; the expression levels of all the genes, with the exception of P57, were reduced in most of the diseased muscle tissues. These results imply that the abnormal expression of these myogenesis-related genes may contribute to concomitant strabismus.

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

“…32 Downregulation of PAX7 is consistent with alteration of myogenesis-related genes such as MYOD1 , myosins, and filament-related muscle proteins (see proteomics, microarray data, 21 and qPCR data 22 ).…”

“…We found that the large majority of relevant ligands, receptors, and transcription factors were expressed in the tendon compartment (Table 2), while a smaller number were primarily expressed in muscle, along with genes known to be expressed in muscle, such as MUSK , PAX7 , and MYOD1 . 22,32 Interestingly, several members of the same family of genes were expressed primarily in either tendon or muscle, but very few were equally distributed in both, indicating specialized compartment-specific functions of distinct members (e.g., MMP2 in tendon, MMP9 in muscle). In addition, some ligands were expressed in one compartment while their receptors were expressed in the other compartment, suggesting that ligands produced in one compartment (e.g., muscle) signal to receptors in the other compartment (e.g., tendon).…”

“…Previous studies on strabismic muscles have either examined small numbers of proteins 13,33,34 or various numbers of genes, 21,22 or a small number of proteins along with genes, but without normal controls. 31 Our study was designed to reveal major changes in protein and gene expression that may contribute to the implementation of adaptive responses.…”

“…33,34 While levels of these proteins were too low for quantification in our proteomic samples, our current study's and other studies' gene expression data confirmed that PAX7 and MYOD1 were significantly reduced at the transcript level. 22 …”

“…Recent work has shown that strabismic muscles display alterations in their gene expression for myosins, myogenic regulatory factors, as well as the extracellular matrix (ECM). 21,22 …”