6533b7d9fe1ef96bd126c3ca
RESEARCH PRODUCT
Deletion of myosin VI causes slow retinal optic neuropathy and age-related macular degeneration (AMD)-relevant retinal phenotype
Kerstin Nagel-wolfrumLukas RüttigerUlrike ZimmermannCorinna GleiserTimm SchubertWibke SingerFrançois Paquet-durandN. RiegerNicole WeisschuhChristoph FranzBernd WissingerBernhard HirtMarlies KnipperUwe WolfrumPeter HeiduschkaPeter HeiduschkaAyse SahabogluGordon EskeKarin Rohbocksubject
Genotypegenetic structuresOuter retinaTranslocator protein TSPOOuter plexiform layermacromolecular substancesBiologyRetinaPhotoreceptor cellMouse modelStereociliaMacular DegenerationMiceCellular and Molecular Neurosciencechemistry.chemical_compoundOptic Nerve DiseasesMyosinmedicineAnimalsBipolar cellMolecular BiologyPharmacologyRetinaRetinal pigment epitheliumMyosin Heavy ChainsNeurodegenerationInner retinaChoriocapillarisRetinalCell BiologyAnatomyMacular degenerationmedicine.diseaseSynapseeye diseasesCell biologyMice Inbred C57BLmedicine.anatomical_structurechemistryMolecular MedicineMicrogliasense organsGene DeletionResearch ArticlePhotoreceptor Cells Vertebratedescription
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. Electronic supplementary material The online version of this article (doi:10.1007/s00018-015-1913-3) contains supplementary material, which is available to authorized users.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-05-01 | Cellular and Molecular Life Sciences |