Extraocular Muscle Structure and Function

  • Linda K. McLoon
  • Christy L. Willoughby
  • Francisco H. Andrade
Chapter

Abstract

It has become increasingly clear that skeletal muscles are not all the same, but have significant differences in terms of embryological development, fiber type, physiological properties, metabolic properties, and disease profile. If one thinks about skeletal muscle as a continuum from the least to most complex, with the leg muscle soleus at one end, the extraocular muscles (EOMs) would be at the other end. The combination of its unusual properties compared to other skeletal muscles has resulted in the suggestion that the EOM represent a distinct allotype (Hoh and Hughes 1988). The goal of this chapter is to summarize the characteristics of the EOM that make them so unique amongst skeletal muscles.

Keywords

Fatigue Migration Depression Lactate Adduct 

Notes

Acknowledgements

Supported by NIH grant EY015313, the Minnesota Lions and Lionessess, and an unrestricted grant to the Department of Ophthalmology from Research to Prevent Blindness Inc.

References

  1. Alvarado-Mallart RM, Pincon-Raymond M (1976) Nerve endings on the intramuscular tendons of cat extraocular muscles. Neurosci Lett 2:121–125PubMedCrossRefGoogle Scholar
  2. Anderson BC, Christiansen SP, Grandt S, Grange RW, McLoon LW (2006) Increased extraocular muscle strength with direct injection of insulin-like growth factor-1. Invest Ophthalmol Vis Sci 47:2461–2467PubMedCrossRefGoogle Scholar
  3. Andrade FH, McMullen CA (2006) Lactate is a metabolic substrate that sustains extraocular function. Pflugers Arch 452:102–108PubMedCrossRefGoogle Scholar
  4. Andrade FH, McMullen CA, Rumbaut RE (2005) Mitochondria are fast Ca2+ sinks in rat extraocular muscles: a novel regulatory influence on contractile function and metabolism. Invest Ophthalmol Vis Sci 205(46):4541–4547CrossRefGoogle Scholar
  5. Antunes-Foschini RM, Ramalho FS, Ramalho LN, Bicas HE (2006) Increased frequency of activated satellite cells in overacting inferior oblique muscles from humans. Invest Ophthalmol Vis Sci 47:3360–3365PubMedCrossRefGoogle Scholar
  6. Antunes-Foschini RM, Miyashita D, Bicas HE, McLoon LK (2008) Activated satellite cells in medial rectus of patients with strabismus. Invest Ophthalmol Vis Sci 49:215–220PubMedCrossRefGoogle Scholar
  7. Asmussen G, Gaunitz U (1981) Mechanical properties of the isolated inferior oblique muscle of the rabbit. Pflugers Arch 392:183–190PubMedCrossRefGoogle Scholar
  8. Asmussen G, Traub I, Pette D (1993) Electrophoretic analysis of myosin heavy chain isoform patterns in extraocular muscles of the rat. FEBS Lett 335:243–245PubMedCrossRefGoogle Scholar
  9. Asmussen G, Punkt K, Bartsch B, Soukup T (2008) Specific metabolic properties of rat oculorotatory extraocular muscles can be linked to their low force requirements. Invest Ophthalmol Vis Sci 49:4866–4871CrossRefGoogle Scholar
  10. Bicer S, Reiser PJ (2009) Myosin isoform expression in dog rectus muscles: patterns of global and orbital layers and among single fibers. Invest Ophthalmol Vis Sci 50:157–167PubMedCrossRefGoogle Scholar
  11. Bohnsack BL, Gallina D, Thompson H, Kasprick DS, Lucarelli MJ, Dootz G, Nelson C, McGonnell IM, Kahana A (2011) Development of extraocular muscles requires early signals from periocular neural crest and the developing eye. Arch Ophthalmol 129:1030–1041PubMedCrossRefGoogle Scholar
  12. Bottinelli R, Canepari M, Pellegrino MA, Reggiani C (1996) Force-velocity properties of human skeletal muscle fibres: myosin heavy chain isoform and temperature dependence. J Physiol 495:573–586PubMedGoogle Scholar
  13. Briggs MM, Schachat F (2002) The superfast extraocular muscle myosin (MYH13) is localized to the innervation zone in both the global and orbital layers of rabbit extraocular muscle. J Exp Biol 205:3133–3142PubMedGoogle Scholar
  14. Briggs MM, Jacoby J, Davidowitz J, Schachat FH (1988) Expression of a novel combination of fast and slow troponin T isoforms in rabbit extraocular muscles. J Muscle Res Cell Motil 9:241–247PubMedCrossRefGoogle Scholar
  15. Caiozzo VJ, Haddad F, Baker M, McCue S, Baldwin KM (2000) MHC polymorphism is rodent plantaris muscle: effects of mechanical overload and hypothyroidism. Am J Physiol Cell Physiol 278:C709–C717PubMedGoogle Scholar
  16. Caiozzo VJ, Baker MJ, Huang K, Chou H, Wu YZ, Baldwin KM (2003) Single-fiber myosin heavy chain polymorphism: how many patterns and what proportions? Am J Physiol Regul Integr Comp Physiol 285:R570–R580PubMedGoogle Scholar
  17. Celio MR, Heizmann CW (1982) Calcium-binding protein parvalbumin is associated with fast contracting muscle fibres. Nature 297:504–506PubMedCrossRefGoogle Scholar
  18. Christiansen SP, McLoon LK (2006) The effect of resection on satellite cell activity in extraocular muscle. Invest Ophthalmol Vis Sci 47:605–613PubMedCrossRefGoogle Scholar
  19. Christiansen SP, Antunes-Foschini RS, McLoon LK (2010) Effect of recession versus tenotomy surgery without recession in adult rabbit extraocular muscle. Invest Ophthalmol Vis Sci 51:5646–5656PubMedCrossRefGoogle Scholar
  20. Close RI, Luff AR (1974) Dynamic properties of inferior rectus muscle of the rat. J Physiol 236:259–270PubMedGoogle Scholar
  21. Croes SA, Baryshnikova LM, Kaluskar SS, von Bartheld CS (2007) Acute and long-term effects of botulinum neurotoxin on the function and structure of developing extraocular muscles. Neurobiol Dis 25:649–664PubMedCrossRefGoogle Scholar
  22. Das V (2012) Motor control and biomechanics. In: McLoon LK, Andrade F (eds) Craniofacial muscles. Springer, New YorkGoogle Scholar
  23. Davidowitz J, Philips G, Breinin GM (1977) Organization of the orbital surface layer in rabbit superior rectus. Invest Ophthalmol Vis Sci 16:711–729PubMedGoogle Scholar
  24. Davidowitz J, Philips G, Breinin GM (1980) Variation of mitochondrial volume fraction along multiply innervated fibers in rabbit extraocular muscle. Tissue Cell 12(3):449–457PubMedCrossRefGoogle Scholar
  25. Diehl AG, Zareparsi S, Qian M, Khanna R, Angeles R, Gage PJ (2006) Extraocular muscle morphogenesis and gene expression are regulated by Pitx2 gene dose. Invest Ophthalmol Vis Sci 47:1785–1793PubMedCrossRefGoogle Scholar
  26. Feng CY, von Bartheld CS (2011) Expression of insulin-like growth factor 1 isoforms in the rabbit oculomotor system. Growth Horm IGF Res 21:228–232PubMedCrossRefGoogle Scholar
  27. Fischer MD, Gorospe JR, Felder E, Bogdanovich S, Pedrosa-Domellöf F, Ahima RS, Rubinstein NA, Hoffman EP, Khurana TS (2002) Expression profiling reveals metabolic and structural components of extraocular muscles. Physiol Genomics 9:71–84PubMedGoogle Scholar
  28. Frueh BR, Gregorevic P, Williams DA, Lynch GS (2001) Specific force of the rat extraocular muscles, levator, and superior rectus, measured in situ. J Neurophysiol 85:1027–1032PubMedGoogle Scholar
  29. Fuchs AF, Binder MD (1983) Fatigue resistance of human extraocular muscles. J Neurophysiol 49:28–34PubMedGoogle Scholar
  30. Fuchs AF, Scudder CA, Kaneko CRS (1988) Discharge patterns and recruitment order of identified motoneurons and internuclear neurons in the monkey abducens nucleus. J Neurophysiol 60:1874–1895PubMedGoogle Scholar
  31. Goding GS, Al-Sharif K, McLoon LK (2005) Myonuclear addition to uninjured laryngeal myofibers in adult rabbits. Ann Otol Rhinol Laryngol 114:552–557PubMedGoogle Scholar
  32. Goldberg SJ, Wilson KE, Shall MS (1997) Summation of extraocular motor unit tensions in the lateral rectus muscle of the cat. Muscle Nerve 20:1229–1235PubMedCrossRefGoogle Scholar
  33. Harel I, Tzahor E (2012) Development of craniofacial muscles. In: McLoon LK, Andrade F (eds) Craniofacial muscles. Springer, New YorkGoogle Scholar
  34. Harrison AR, Anderson BC, Thompson LV, McLoon LK (2007) Myofiber length and three-dimensional localization of NMJs in normal and botulinum toxin treated adult extraocular muscles. Invest Ophthalmol Vis Sci 48:3594–3601PubMedCrossRefGoogle Scholar
  35. Hoh JF, Hughes S (1988) Myogenic and neurogenic regulation of myosin gene expression in cat jaw closing muscles regenerating in fast and slow limb muscle beds. J Muscle Res Cell Motil 9:59–72PubMedCrossRefGoogle Scholar
  36. Horton RM, Manfredi AA, Conti-Tronconi BM (1993) The embryonic gamma subunit of the nicotinic acetylcholine receptor is expressed in adult extraocular muscle. Neurology 43:983–986PubMedCrossRefGoogle Scholar
  37. Jacoby J, Chiarandini DJ, Stefani E (1989a) Electrical properties and innervation of fibers in the orbital layer of rat extraocular muscles. J Neurophysiol 61:116–125PubMedGoogle Scholar
  38. Jacoby J, Ko K, Weiss C, Rushbrook JI (1989b) Systematic variation in myosin expression along extraocular muscle fibres of the adult rat. J Muscle Res Cell Motil 11:25–40CrossRefGoogle Scholar
  39. Kallestad KM, Hebert SL, McDonald AA, Daniel ML, Cu SR, McLoon LK (2011) Sparing of the extraocular muscle in aging and dystrophic skeletal muscle: a myogenic precursor cell hypothesis. Exp Cell Res 317:873–885PubMedCrossRefGoogle Scholar
  40. Kaminski HJ, Kusner LL, Block CH (1996) Expression of acetylcholine receptor isoforms at extraocular muscle endplates. Invest Ophthalmol Vis Sci 37:345–351PubMedGoogle Scholar
  41. Khurana TS, Prendergast RA, Alameddine HS, Tome FMS, Fardeau M, Arahata K, Sugita H, Kunkel LM (1995) Absence of extraocular muscle pathology in Duchenne’s muscular dystrophy: role for calcium homeostasis in extraocular muscle sparing. J Exp Med 182:467–475PubMedCrossRefGoogle Scholar
  42. Kjellgren D, Ryan M, Ohlendieck K, Thornell LE, Pedrosa-Domellöf F (2003a) Sarco(endo)plasmic reticulum Ca2+ ATPases (SERCA1 and 2) in human extraocular muscles. Invest Ophthalmol Vis Sci 44:5057–5062PubMedCrossRefGoogle Scholar
  43. Kjellgren D, Thornell LE, Anderson J, Pedrosa-Domellöf F (2003b) Myosin heavy chain isoforms in human extraocular muscles. Invest Ophthalmol Vis Sci 44:1419–1425PubMedCrossRefGoogle Scholar
  44. Kjellgren D, Thornell LE, Virtanen I, Pedrosa-Domellof (2004) Laminin isoforms in human extraocular muscles. Invest Ophthalmol Vis Sci 45:4233–4239PubMedCrossRefGoogle Scholar
  45. Kjellgren D, Stal P, Larsson L, Fuerst D, Pedrosa-Domellöf F (2006) Uncoordinated expression of myosin heavy chains and myosin-binding protein C isoforms in human extraocular muscles. Invest Ophthalmol Vis Sci 47:4188–4193PubMedCrossRefGoogle Scholar
  46. Kupfer C (1960) Motor innervation of extraocular muscle. J Physiol 153:522–526PubMedGoogle Scholar
  47. Mascarello F, Carpene E, Veggetti A, Rowlerson A, Jenny E (1982) The tensor tympani muscle of cat and dog contains IIM and slow-tonic fibres: an unusual combination of fibre types. J Muscle Res Cell Motil 3:363–374PubMedCrossRefGoogle Scholar
  48. Mayr R (1971) Structure and distribution of fibre types in the external eye muscles of the rat. Tissue Cell 3:433–462PubMedCrossRefGoogle Scholar
  49. McLoon LK, Wirtschafter JD (2002) Continuous myonuclear addition to single extraocular myofibers in uninjured adult rabbits. Muscle Nerve 25:348–358PubMedCrossRefGoogle Scholar
  50. McLoon LK, Wirtschafter JD (2003) Activated satellite cells in extraocular muscles of normal, adult monkeys and humans. Invest Ophthalmol Vis Sci 44:1927–1932PubMedCrossRefGoogle Scholar
  51. McLoon LK, Rios L, Wirtschafter JD (1999) Complex three-dimensional patterns of myosin isoform expression: differences between and within specific extraocular muscles. J Muscle Res Cell Motil 20:771–783PubMedCrossRefGoogle Scholar
  52. McLoon LK, Rowe J, Wirtschafter JD, McCormick KM (2004) Continuous myofiber remodeling in uninjured extraocular myofibers: myonuclear turnover and evidence for apoptosis. Muscle Nerve 29:707–715PubMedCrossRefGoogle Scholar
  53. McLoon LK, Park H, Kim JH, Pedrosa-Domellöf F, Thompson LV (2011) A continuum of myofibers in adult rabbit extraocular muscle: force, shortening velocity, and patterns of myosin heavy chain co-localization. J Appl Physiol 111:1178–1189PubMedCrossRefGoogle Scholar
  54. Milller JM, Bockisch CJ, Pavlovski DS (2002) Missing lateral rectus force and absence of medial rectus co-contraction in ocular convergence. J Neurophysiol 87:2421–2433Google Scholar
  55. Moncman CL, Andrade FH (2010) Nonmuscle myosin IIB, a sarcomeric component in the extraocular muscles. Exp Cell Res 316:1958–1965PubMedCrossRefGoogle Scholar
  56. Pachter BR (1983) Rat extraocular muscle. 1. Three dimensional cytoarchitecture, component fibre populations and innervation. J Anat 137:143–159PubMedGoogle Scholar
  57. Pachter BR (1984) Rat extraocular muscle. 3. Histochemical variability along the length of multiply-innervated fibers of the orbital surface layer. Histochemistry 80:535–538PubMedGoogle Scholar
  58. Pachter BR, Colbjornsen C (1983) Rat extraocular muscle. 2. Histochemical fibre types. J Anat 137:161–170PubMedGoogle Scholar
  59. Pachter BR, Davidowitz A, Breinin GM (1976) Light and electron microscopic serial analysis of mouse extraocular muscle: morphology, innervation and topographical organization of component fiber populations. Tissue Cell 8:547–560PubMedCrossRefGoogle Scholar
  60. Patel SP, Gamboa JL, McMullen CA, Rabchevsky A, Andrade FH (2009) Lower respiratory capacity in extraocular muscle mitochondria: evidence for intrinsic differences in mitochondrial composition and function. Invest Ophthalmol Vis Sci 50:180–186PubMedCrossRefGoogle Scholar
  61. Pedrosa-Domellöf F (2012) Extraocular muscle response to neuromuscular diseases and specific pathologies. In: McLoon LK, Andrade F (eds) Craniofacial muscles. Springer, New YorkGoogle Scholar
  62. Pedrosa-Domellöf F, Eriksson PO, Butler-Browne GS, Thornell LE (1992) Expression of alpha-cardiac myosin heavy chain in mammalian skeletal muscle. Experientia 48:491–494PubMedCrossRefGoogle Scholar
  63. Porter JD, Hauser KF (1993) Survival of extraocular muscle in long-term organotypic culture: differential influence of appropriate and inappropriate motoneurons. Dev Biol 160:39–50PubMedCrossRefGoogle Scholar
  64. Porter JD, Khanna S, Kaminski HJ, Rao JS, Merriam AP, Richmonds CR, Leahy P, Li J, Andrade FH (2001) Extraocular muscle is defined by a fundamentally distinct gene expression profile. Proc Natl Acad Sci U S A 98:12062–12067PubMedCrossRefGoogle Scholar
  65. Prsa M, Dicke PW, Their P (2010) The absence of eye muscle fatigue indicates that the nervous system compensates for non-motor disturbances of oculomotor function. J Neurosci 30:15834–15842PubMedCrossRefGoogle Scholar
  66. Rossi AC, Mammucari C, Argentini C, Reggiani C, Schiaffino S (2010) Two novel/ancient myosins in mammalian skeletal muscles: MYH14/7b and MYH15 are expressed in extraocular muscles and muscle spindles. J Physiol 588:353–364PubMedCrossRefGoogle Scholar
  67. Rubinstein NA, Hoh JF (2000) The distribution of myosin heavy chain isoforms among rat extraocular muscle fiber types. Invest Ophthalmol Vis Sci 41:3391–3398PubMedGoogle Scholar
  68. Shall MS, Dimitrova DM, Goldberg SJ (2003) Extraocular motor unit and whole-muscle contractile properties in the squirrel monkey. Summation of forces and fiber morphology. Exp Brain Res 151:338–345PubMedCrossRefGoogle Scholar
  69. Shinners MJ, Goding GS, McLoon LK (2006) Effect of recurrent laryngeal nerve section on the laryngeal muscles of adult rabbits. Otolaryngol Head Neck Surg 134:413–418PubMedCrossRefGoogle Scholar
  70. Spencer RF, McNeer KW (1987) Botulinum toxin paralysis of adult monkey extraocular muscle. Structural alterations in orbital, singly innervated muscle fibers. Arch Ophthalmol 105:1703–1711PubMedCrossRefGoogle Scholar
  71. Stirn Kranjc B, Sketelj J, D’Albis A, Ambroz M, Erzen I (2000) Fibre types and myosin heavy chain expression in the ocular medial rectus of the adult rat. J Muscle Res Cell Motil 21:753–761CrossRefGoogle Scholar
  72. Stirn Kranjc B, Sketelj J, D’Albis A, Erzen I (2001) Long term changes in myosin heavy chain composition after botulinum toxin A injection into rat medial rectus muscle. Invest Ophthalmol Vis Sci 42:3158–3164Google Scholar
  73. Stirn Kranjc B, Smerdu V, Erzen I (2009) Histochemical and immunohistochemical profile of human and rat ocular medial rectus muscles. Graefes Arch Clin Exp Ophthalmol 247:1505–1515PubMedCrossRefGoogle Scholar
  74. Tajbakhsh S, Rocancout D, Cossu G, Buckingham M (1997) Redefining the genetic hierarchies controlling skeletal myogenesis: Pax-3 and myf-5 act upstream of MyoD. Cell 89:127–138PubMedCrossRefGoogle Scholar
  75. Toniolo L, Maccatrozzo L, Patruno M, Pavan E, Caliario F, Rossi R, Rinaldi C, Canepari M, Reggiani C, Mascarello F (2007) Fiber types in canine muscles: myosin isoform expression and functional characterization. Am J Physiol Cell Physiol 292:1915–1926CrossRefGoogle Scholar
  76. Ugalde I, Christiansen SP, McLoon LK (2005) Botulinum toxin treatment of extraocular muscles in rabbits results in increased myofiber remodeling. Invest Ophthalmol Vis Sci 46:4114–4120PubMedCrossRefGoogle Scholar
  77. Wasicky R, Ziya-Ghazvini F, Blumer R, Lukas JR, Mayr R (2000) Muscle fiber types of human extraocular muscles: a histochemical and immunohistochemical study. Invest Ophthalmol Vis Sci 41:980–990PubMedGoogle Scholar
  78. Wieczorek DF, Periasamy M, Butler-Browne GS, Whalen RG, Nadal-Ginard B (1985) Co-expression of multiple myosin heavy chain genes, in addition to a tissue-specific one, in extraocular musculature. J Cell Biol 101:618–629PubMedCrossRefGoogle Scholar
  79. Zacharias AL, Lewandoski M, Rudnicki MA, Gage PJ (2011) Pitx2 is an upstream activator of extraocular myogenesis and survival. Dev Biol 349:395–405PubMedCrossRefGoogle Scholar
  80. Zeiger U, Mitchell CH, Khurana TS (2010) Superior calcium homeostasis of extraocular muscles. Exp Eye Res 91:613–622PubMedCrossRefGoogle Scholar
  81. Zhou Y, Cheng G, Dieter L, Hjalt TA, Andrade FH, Stahl JS, Kaminski HJ (2009) An altered phenotype in a conditional knockout of Pitx2 in extraocular muscle. Invest Ophthalmol Vis Sci 50:4531–4541PubMedCrossRefGoogle Scholar
  82. Zhou Y, Liu D, Kaminski HJ (2010) Myosin heavy chain expression in mouse extraocular muscle: more complex than expected. Invest Ophthalmol Vis Sci 51:6355–6363PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Linda K. McLoon
    • 1
  • Christy L. Willoughby
    • 2
  • Francisco H. Andrade
    • 3
  1. 1.Department of OphthalmologyUniversity of MinnesotaMinneapolisUSA
  2. 2.Departments of Ophthalmology and NeuroscienceUniversity of MinnesotaMinneapolisUSA
  3. 3.Department of PhysiologyUniversity of KentuckyLexingtonUSA

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