title: Altered Protein Composition and Gene Expression in Strabismic Human Extraocular Muscles and Tendons.
abstract: OBJECTIVE
  To determine whether structural protein composition and expression of key regulatory genes are altered in strabismic human extraocular muscles.
  
  
  METHODS
  Samples 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.
  
  
  RESULTS
  Strabismic 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.
  
  
  CONCLUSIONS
  Quantification 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.
authors: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, United States.
authors: Andrea B
authors: AB
authors: Agarwal
authors: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, United States.
authors: Cheng-Yuan
authors: CY
authors: Feng
authors: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, United States.
authors: Amy L
authors: AL
authors: Altick
authors: Mick Hitchcock Nevada Proteomics Center, University of Nevada, Reno, Nevada, United States.
authors: David R
authors: DR
authors: Quilici
authors: Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.
authors: Dan
authors: D
authors: Wen
authors: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, United States 4Sierra Eye Associates, Reno, Nevada, United States.
authors: L Alan
authors: LA
authors: Johnson
authors: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nevada, United States.
authors: Christopher S
authors: CS
authors: von Bartheld
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics*; D009801:Oculomotor Muscles / Q000378:metabolism* / Q000473:pathology; D040901:Proteomics / Q000379:methods; D012313:RNA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013285:Strabismus / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013710:Tendons / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D009124:Muscle Proteins; D012313:RNA