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Laminin isoforms in human extraocular muscles
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Ophthalmology.
2004 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, Vol. 45, no 12, 4233-4239 p.Article in journal (Refereed) Published
Abstract [en]

PURPOSE: To determine the laminin isoform composition of the basement membranes (BMs) in the human extraocular muscles (EOMs) and relate it to the fact that EOMs are spared in laminin alpha2-chain-deficient congenital muscular dystrophy. METHODS: Samples from adult human EOMs and limb muscle were processed for immunocytochemistry, with monoclonal antibodies against laminin chains (Ln) alpha1 to -5, beta1 and -2, and gamma1. Neuromuscular junctions (NMJs) were identified with acetylcholinesterase reaction. The capillary density was measured in sections stained with anti-Lnalpha5. RESULTS: The extrasynaptic BM of the EOM muscle fibers contained Lnalpha2, -beta1, -beta2, and -gamma1, and, in contrast to limb muscle, it also contained Lnalpha4 and -alpha5, to some extent. The distinct laminin composition of the EOMs was confirmed by the presence of Lutheran protein, an alpha5-chain-specific receptor not found in limb muscle. At the NMJs, there was increased expression of Lnalpha4 and expression of Lnalpha2, -alpha5, -beta1, -beta2, and -gamma1 was also maintained. The capillary density was very high (1050 +/- 190 capillaries/mm(2)) in the EOMs and significantly (P < 0.05) higher in the orbital (1170 +/- 180 capillaries/mm(2)) than in the global (930 +/- 110 capillaries/mm(2)) layer. CONCLUSIONS: The human EOMs showed important differences in laminin isoform composition and capillary density when compared with human limb muscle and muscles of other species. The presence of additional laminin isoforms other than laminin-2 in the BM of the extrasynaptic sarcolemma could partly explain the sparing of the EOMs in Lnalpha2-deficient congenital muscular dystrophy.

Place, publisher, year, edition, pages
Association for Research in Vision and Ophthalmology , 2004. Vol. 45, no 12, 4233-4239 p.
Keyword [en]
Adolescent, Adult, Aged, Aged; 80 and over, Basement Membrane/metabolism, Capillaries/anatomy & histology, Extremities, Histocytochemistry, Humans, Immunohistochemistry, Infant; Newborn, Laminin/*metabolism, Middle Aged, Muscle Fibers/metabolism, Muscle; Skeletal/blood supply/metabolism, Oculomotor Muscles/blood supply/*metabolism, Protein Isoforms/metabolism, Receptors; Laminin/metabolism, Sarcolemma/metabolism, Tissue Distribution
National Category
URN: urn:nbn:se:umu:diva-12678DOI: 10.1167/iovs.04-0456PubMedID: 15557425OAI: diva2:152349
Available from: 2008-01-10 Created: 2008-01-10 Last updated: 2013-12-12Bibliographically approved
In thesis
1. Human extraocular muscles: molecular diversity of a unique muscle allotype
Open this publication in new window or tab >>Human extraocular muscles: molecular diversity of a unique muscle allotype
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Introduction: The extraocular muscles (EOMs) are considered a separate class of skeletal muscle, allotype. Myosin is the major contractile protein in muscle. The myosin heavy chain (MyHC) isoforms are the best molecular markers of functional heterogeneity of muscle fibers. The relaxation rate, reflects the rate at which Ca2+ is transported back into the sarcoplasmic reticulum (SR) mostly by SR Ca2+ATPase (SERCA). Myosin binding protein C (MyBP-C), plays a physiological role in regulating contraction. The laminins (Ln) are the major non-collagenous components of the basement membrane (BM) surrounding muscle fibers and are important for muscle fiber integrity.

Methods: Adult human EOMs were studied with SDS-PAGE, immunoblots and immunocytochemistry, the latter with antibodies against six MyHC, 2 SERCA, 2 MyBP-C and 8 laminin chain isoforms. The capillary density was also determined.

Results: Most fibers contained a mixture of MyHC isoforms. Three major groups of fibers could be distinguished. Fast fibers that stained with anti-MyHCIIa, slow fibers that stained with anti-MyHCI and MyHCeompos/MyHCIIaneg-fibers that stained with neither of these antibodies but with anti-MyHCI+IIa+eom and anti-MyHCeom. A majority of the fibers contained both SERCA1 and 2 whereas 1% were unstained with both antibodies. Biochemically SERCA2 was more abundant than SERCA1. MyBP-Cfast was not present in the EOMs and MyBP-Cslow was only detected immunocytochemically. The extrasynaptical BM of the EOM muscle fibers contained Lna2, b1, b2, g1, a4 and a5 chains. The capillary density in the EOMs was very high (1050 +/-190 capillaries/mm2) and significantly (p<0.05) higher in the orbital than in the global layer.

Conclusions: The co-existence of complex mixtures of several crucial protein isoforms provide the human EOMs with a unique molecular portfolio that a) allows a highly specific fine-tuning regime of contraction and relaxation, and b) imparts structural properties that are likely to contribute to protection against certain neuromuscular diseases.

Place, publisher, year, edition, pages
Umeå: Umeå university, 2004. 51 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 890
Ophtalmology, extraocular, muscle, myosin, protein c, laminin, serca, immunocytochemistry, human, Oftalmiatrik
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Research subject
urn:nbn:se:umu:diva-260 (URN)91-7305-638-3 (ISBN)
Public defence
2004-05-28, E04, 6E, Norrlands Universitetssjukhus, Umeå, 13:15
Available from: 2004-05-05 Created: 2004-05-05 Last updated: 2011-04-08Bibliographically approved

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