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

Wim H Quint; Kirke C D Tadema; Erik de Vrieze; Rachel M Lukowicz; Sanne Broekman; Beerend H J Winkelman; Melanie Hoevenaars; H Martijn de Gruiter; Erwin van Wijk; Frank Schaeffel; Magda Meester-Smoor; Adam C Miller; Rob Willemsen; Caroline C W Klaver; Adriana I Iglesias

doi:10.1038/s42003-021-02185-z

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

Wim H Quint, Kirke C D Tadema, Erik de Vrieze, Rachel M Lukowicz, Sanne Broekman, Beerend H J Winkelman, Melanie Hoevenaars, H Martijn de Gruiter, Erwin van Wijk, Frank Schaeffel, Magda Meester-Smoor, Adam C Miller, Rob Willemsen, Caroline C W Klaver, Adriana I Iglesias

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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.

Originele taal-2	Engels
Pagina's (van-tot)	676
Tijdschrift	Communications Biology
Volume	4
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1038/s42003-021-02185-z
Status	Gepubliceerd - 2021

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Quint, W. H., Tadema, K. C. D., de Vrieze, E., Lukowicz, R. M., Broekman, S., Winkelman, B. H. J., Hoevenaars, M., de Gruiter, H. M., van Wijk, E., Schaeffel, F., Meester-Smoor, M., Miller, A. C., Willemsen, R., Klaver, C. C. W., & Iglesias, A. I. (2021). Loss of Gap Junction Delta-2 (GJD2) gene orthologs leads to refractive error in zebrafish. Communications Biology, 4(1), 676. https://doi.org/10.1038/s42003-021-02185-z

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title = "Loss of Gap Junction Delta-2 (GJD2) gene orthologs leads to refractive error in zebrafish",

abstract = "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.",

author = "Quint, {Wim H} and Tadema, {Kirke C D} and {de Vrieze}, Erik and Lukowicz, {Rachel M} and Sanne Broekman and Winkelman, {Beerend H J} and Melanie Hoevenaars and {de Gruiter}, {H Martijn} and {van Wijk}, Erwin and Frank Schaeffel and Magda Meester-Smoor and Miller, {Adam C} and Rob Willemsen and Klaver, {Caroline C W} and Iglesias, {Adriana I}",

year = "2021",

doi = "10.1038/s42003-021-02185-z",

language = "English",

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journal = "Communications Biology",

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Quint, WH, Tadema, KCD, de Vrieze, E, Lukowicz, RM, Broekman, S, Winkelman, BHJ, Hoevenaars, M, de Gruiter, HM, van Wijk, E, Schaeffel, F, Meester-Smoor, M, Miller, AC, Willemsen, R, Klaver, CCW & Iglesias, AI 2021, 'Loss of Gap Junction Delta-2 (GJD2) gene orthologs leads to refractive error in zebrafish', Communications Biology, vol. 4, nr. 1, blz. 676. https://doi.org/10.1038/s42003-021-02185-z

TY - JOUR

T1 - Loss of Gap Junction Delta-2 (GJD2) gene orthologs leads to refractive error in zebrafish

AU - Quint, Wim H

AU - Tadema, Kirke C D

AU - de Vrieze, Erik

AU - Lukowicz, Rachel M

AU - Broekman, Sanne

AU - Winkelman, Beerend H J

AU - Hoevenaars, Melanie

AU - de Gruiter, H Martijn

AU - van Wijk, Erwin

AU - Schaeffel, Frank

AU - Meester-Smoor, Magda

AU - Miller, Adam C

AU - Willemsen, Rob

AU - Klaver, Caroline C W

AU - Iglesias, Adriana I

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1038/s42003-021-02185-z

DO - 10.1038/s42003-021-02185-z

M3 - Article

C2 - 34083742

SN - 2399-3642

VL - 4

SP - 676

JO - Communications Biology

JF - Communications Biology

IS - 1

ER -

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

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