Loss of Gap Junction Delta-2 (GJD2) gene orthologs leads to refractive error in zebrafish.

Autor: Quint WH; Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands. w.quint@erasmusmc.nl.; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands. w.quint@erasmusmc.nl., Tadema KCD; Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands., de Vrieze E; Department of Otorhinolaryngology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, Netherlands., Lukowicz RM; Institute of Neuroscience, University of Oregon, Eugene, United States., Broekman S; Department of Otorhinolaryngology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, Netherlands., Winkelman BHJ; Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.; Department of Cerebellar Coordination and Cognition, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands., Hoevenaars M; Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands., de Gruiter HM; Optical Imaging Centre, Erasmus Medical Center, Rotterdam, The Netherlands., van Wijk E; Department of Otorhinolaryngology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, Netherlands., Schaeffel F; Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany.; Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland., Meester-Smoor M; Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands., Miller AC; Institute of Neuroscience, University of Oregon, Eugene, United States., Willemsen R; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands., Klaver CCW; Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.; Institute of Molecular and Clinical Ophthalmology Basel, Basel, Switzerland.; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.; Department of Ophthalmology, Radboud University Medical Center, Nijmegen, The Netherlands., Iglesias AI; Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands. a.iglesiasgonzalez@erasmusmc.nl.; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands. a.iglesiasgonzalez@erasmusmc.nl.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2021 Jun 03; Vol. 4 (1), pp. 676. Date of Electronic Publication: 2021 Jun 03.
DOI: 10.1038/s42003-021-02185-z
Abstrakt: Myopia is the most common developmental disorder of juvenile eyes, and it has become an increasing cause of severe visual impairment. The GJD2 locus has been consistently associated with myopia in multiple independent genome-wide association studies. However, despite the strong genetic evidence, little is known about the functional role of GJD2 in refractive error development. Here, we find that depletion of gjd2a (Cx35.5) or gjd2b (Cx35.1) orthologs in zebrafish, cause changes in the biometry and refractive status of the eye. Our immunohistological and scRNA sequencing studies show that Cx35.5 (gjd2a) is a retinal connexin and its depletion leads to hyperopia and electrophysiological changes in the retina. These findings support a role for Cx35.5 (gjd2a) in the regulation of ocular biometry. Cx35.1 (gjd2b) has previously been identified in the retina, however, we found an additional lenticular role. Lack of Cx35.1 (gjd2b) led to a nuclear cataract that triggered axial elongation. Our results provide functional evidence of a link between gjd2 and refractive error.
Databáze: MEDLINE
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