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      Morphological Differences in the Inferior Oblique Muscles from Subjects with Over-elevation in Adduction

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          Abstract

          Purpose

          We examined inferior oblique muscles from subjects with over-elevation in adduction for characteristics that might shed light on the potential mechanisms for their abnormal eye position.

          Methods

          The inferior oblique muscles were obtained at the time of surgery in subjects diagnosed with either primary inferior oblique overaction or Apert syndrome. The muscles were frozen and processed for morphometric analysis of myofiber size, central nucleation, myosin heavy chain (MyHC) isoform expression, nerve density, and numbers of neuromuscular junctions per muscle section.

          Results

          The inferior oblique muscles from subjects with Apert Syndrome were smaller, and had a much more heterogeneous profile relative to myofiber cross-sectional area compared to controls. Increased central nucleation in the Apert syndrome muscles suggested on-going myofiber regeneration or reinnervation over time. Complex changes were seen in the MyHC isoform patterns that would predict slower and more sustained contractions than in the control muscles. Nerve fiber densities were significantly increased compared to controls for the muscles with primary inferior oblique overaction and Apert syndrome that had no prior surgery. The muscles from Apert syndrome subjects as well as those with primary inferior oblique overaction with no prior surgery had significantly elevated numbers of neuromuscular junctions relative to the whole muscle area.

          Conclusions

          The muscles from both sets of subjects were significantly different from control muscles in a number of properties examined. These data support the view that despite similar manifestations of eye misalignment, the potential mechanism behind the strabismus in these subjects is significantly different.

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          Most cited references73

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          Force-velocity relations and myosin heavy chain isoform compositions of skinned fibres from rat skeletal muscle.

          1. This study was performed to assess whether muscle contractile properties are related to the presence of specific myosin heavy chain (MHC) isoforms. 2. Force-velocity relations and MHC isoform composition were determined in seventy-four single skinned muscle fibres from rat soleus, extensor digitorum longus and plantaris muscles. 3. Four groups of fibres were identified according to their MHC isoform composition determined by monoclonal antibodies: type 1 (slow), and types 2A, 2B and 2X (fast). 4. With respect to maximum velocity of shortening (V0), the fibres formed a continuum between 0.35 and 2.84 L/s (muscle lengths per second) at 12 degrees C. V0 in type 1 fibres (slow fibres) was between 0.35 and 0.95 L/s (0.639 +/- 0.038 L/s; mean +/- S.E. of mean). V0 in type 2 fibres (fast fibres) was consistently higher than 0.91 L/s. Ranges of V0 in the three fast fibre types mostly overlapped. Type 2A and 2X fibres had similar mean V0 values (1.396 +/- 0.084 and 1.451 +/- 0.066 L/s respectively); type 2B fibres showed a higher mean V0 value (1.800 +/- 0.109 L/s) than type 2A and 2X fibres. 5. Mean values of a/P0, an index of the curvature of force-velocity relations, allowed us to identify two groups of fibres: a high curvature group comprised of type 1 (mean a/P0, 0.066 +/- 0.007) and 2A (0.066 +/- 0.024) fibres and a low curvature group comprised of type 2B (0.113 +/- 0.013) and 2X (0.132 +/- 0.008) fibres. 6. Maximal power output was lower in slow fibres than in fast fibres, and among fast fibres it was lower in type 2A fibres than in type 2X and 2B. 7. Force per unit cross-sectional area was less in slow fibres than in fast fibres. There was no relation between fibre type and cross-sectional area. 8. The results suggest that MHC composition is just one of the determinants of shortening velocity and of other muscle contractile properties.
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            Apert syndrome mutations in fibroblast growth factor receptor 2 exhibit increased affinity for FGF ligand.

            Dominantly acting mutations of the fibroblast growth factor (FGF) receptor 2 (FGFR2) gene have been implicated in various craniosynostosis syndromes. Apert syndrome, characterized in addition by syndactyly of the limbs, involves specific mutations at two adjacent residues, Ser252Trp and Pro253Arg, predicted to lie in the linker region between IgII and IgIII of the FGFR2 ligand-binding domain. We have analysed the interaction of FGF ligands with wild-type and Apert-type mutant FGFR2 ectodomains in solution. Wild-type and Apert-type receptors form a complex with FGF ligands with a stoichiometry of 2:2 (ligand:receptor). The kinetics and specificity of ligand binding to wild-type and Apert mutant receptors have been analysed using surface plasmon resonance techniques. This reveals that Apert mutations, compared with wild-type, exhibit a selective decrease in the dissociation kinetics of FGF2, but not of other FGF ligands examined. In contrast, the substitution Ser252Leu in FGFR2, previously observed in several asymptomatic individuals, exhibited wild-type kinetics. These findings indicate that Apert syndrome arises as a result of increased affinity of mutant receptors for specific FGF ligands which leads to activation of signalling under conditions where availability of ligand is limiting.
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              Long-term results of the surgical management of intermittent exotropia.

              To examine long-term surgical success rates (>10 years) for patients with intermittent exotropia and the risk factors for failure of surgery in these patients.
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                Author and article information

                Journal
                Invest Ophthalmol Vis Sci
                Invest. Ophthalmol. Vis. Sci
                iovs
                IOVS
                Investigative Ophthalmology & Visual Science
                The Association for Research in Vision and Ophthalmology
                0146-0404
                1552-5783
                15 June 2020
                June 2020
                : 61
                : 6
                : 33
                Affiliations
                [1 ]Department of Ophthalmology, University of California San Diego, La Jolla, California, United States
                [2 ]Pediatric Ophthalmology & the Center for Adult Strabismus, P.A., Plano, Texas, United States
                [3 ]Retina Foundation of the Southwest, Dallas, Texas, United States
                [4 ]Department of Ophthalmology and Visual Neurosciences and Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota, United States
                Author notes
                Correspondence: Linda K. McLoon, Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Room 374 Lions Research Building, 2001 6th Street SE, Minneapolis, MN 55455, USA; mcloo001@ 123456umn.edu .
                Article
                IOVS-19-29231
                10.1167/iovs.61.6.33
                7415317
                32539136
                3e296f14-9f0c-4c9d-8773-a60850f2d025
                Copyright 2020 The Authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 01 May 2020
                : 30 December 2019
                Page count
                Pages: 11
                Categories
                Eye Movements, Strabismus, Amblyopia and Neuro-Ophthalmology
                Eye Movements, Strabismus, Amblyopia and Neuro-Ophthalmology

                strabismus,extraocular muscle,inferior oblique,inferior oblique overaction,apert syndrome,neuromuscular junctions

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