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Cell Mol Life Sci. 2015 Oct;72(20):3953-69. doi: 10.1007/s00018-015-1913-3. Epub 2015 May 6.

Deletion of myosin VI causes slow retinal optic neuropathy and age-related macular degeneration (AMD)-relevant retinal phenotype.

Author information

1
Werner Reichardt Centre for Integrative Neuroscience (CIN)/Institute for Ophthalmic Research, University of Tübingen, Otfried-Müller-Str. 25, 72076, Tübingen, Germany. timm.schubert@uni-tuebingen.de.
2
Institute of Anatomy, Department of Clinical Anatomy and Cell Analysis, University of Tübingen, Elfriede-Aulhorn-Str. 8, 72076, Tübingen, Germany. corinna.gleiser@klinikum.uni-tuebingen.de.
3
Experimental Vitreoretinal Surgery, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, 72076, Tübingen, Germany. peter.heiduschka@ukmuenster.de.
4
University Eye Hospital Münster, Westfälische Wilhelms-University of Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany. peter.heiduschka@ukmuenster.de.
5
Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany. ch.franz@gmail.com.
6
Institute of Zoology, Cell and Matrix Biology, Johannes Gutenberg University of Mainz, Johann-Joachim-Becher-Weg 11, 55128, Mainz, Germany. nagelwol@uni-Mainz.de.
7
Cell Death Mechanisms Group, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany. ayse.sahaboglu-tekgoez@klinikum.uni-tuebingen.de.
8
Molecular Genetics, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany. nicole.weisschuh@uni-tuebingen.de.
9
Werner Reichardt Centre for Integrative Neuroscience (CIN)/Institute for Ophthalmic Research, University of Tübingen, Otfried-Müller-Str. 25, 72076, Tübingen, Germany. gordon.eske@klinikum.uni-tuebingen.de.
10
Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany. KarinRohbock@yahoo.de.
11
Cell Death Mechanisms Group, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany. norman.rieger@medizin.uni-tuebingen.de.
12
Cell Death Mechanisms Group, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany. francois.paquet-durand@klinikum.uni-tuebingen.de.
13
Molecular Genetics, Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tübingen, Röntgenweg 11, 72076, Tübingen, Germany. wissinger@uni-tuebingen.de.
14
Institute of Zoology, Cell and Matrix Biology, Johannes Gutenberg University of Mainz, Johann-Joachim-Becher-Weg 11, 55128, Mainz, Germany. wolfrum@uni-mainz.de.
15
Institute of Anatomy, Department of Clinical Anatomy and Cell Analysis, University of Tübingen, Elfriede-Aulhorn-Str. 8, 72076, Tübingen, Germany. bernhard.hirt@klinikum.uni-tuebingen.de.
16
Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany. wibke.singer@uni-tuebingen.de.
17
Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany. lukas.ruettiger@uni-tuebingen.de.
18
Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany. ulrike.zimmermann@uni-tuebingen.de.
19
Molecular Physiology of Hearing, Tübingen Hearing Research Centre, Department of Otolaryngology, Head and Neck Surgery, University of Tübingen, Elfriede-Aulhorn-Str. 5, 72076, Tübingen, Germany. marlies.knipper@uni-tuebingen.de.

Abstract

The unconventional myosin VI, a member of the actin-based motor protein family of myosins, is expressed in the retina. Its deletion was previously shown to reduce amplitudes of the a- and b-waves of the electroretinogram. Analyzing wild-type and myosin VI-deficient Snell's Waltzer mice in more detail, the expression pattern of myosin VI in retinal pigment epithelium, outer limiting membrane, and outer plexiform layer could be linked with differential progressing ocular deficits. These encompassed reduced a-waves and b-waves and disturbed oscillatory potentials in the electroretinogram, photoreceptor cell death, retinal microglia infiltration, and formation of basal laminar deposits. A phenotype comprising features of glaucoma (neurodegeneration) and age-related macular degeneration could thus be uncovered that suggests dysfunction of myosin VI and its variable cargo adaptor proteins for membrane sorting and autophagy, as possible candidate mediators for both disease forms.

KEYWORDS:

Bipolar cell; Choriocapillaris; Inner retina; Mouse model; Outer retina; Stereocilia; Synapse; Translocator protein TSPO

PMID:
25939269
PMCID:
PMC4575690
DOI:
10.1007/s00018-015-1913-3
[Indexed for MEDLINE]
Free PMC Article

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