Role of GUCA1C in Primary Congenital Glaucoma and in the Retina: Functional Evaluation in Zebrafish

Área de Genética, Facultad de Medicina de Albacete/Instituto de Investigación en Discapacidades Neurológicas (IDINE), Universidad de Castilla-La Mancha, 02006 Albacete, Spain

Cooperative Research Network on Age-Related Ocular Pathology, Visual and Life Quality (OFTARED), Instituto de Salud Carlos III, 28029 Madrid, Spain

Servicio de Oftalmología, Hospital San Carlos, 28040 Madrid, Spain

⁴

Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, 28040 Madrid, Spain

⁵

Department of Optics, Pharmacology and Anatomy, University of Alicante, 03690 Alicante, Spain

⁶

Department of Physiology, Genetics and Microbiology, University of Alicante, 03690 Alicante, Spain

⁷

Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06510, USA

Author to whom correspondence should be addressed.

Genes 2020, 11(5), 550; https://doi.org/10.3390/genes11050550

Received: 27 March 2020 / Revised: 6 May 2020 / Accepted: 12 May 2020 / Published: 14 May 2020

(This article belongs to the Special Issue Molecular Genetics of Retinal Dystrophies)

View Full-Text Download PDF

Browse Figures

Citation Export

Abstract

Primary congenital glaucoma (PCG) is a heterogeneous, inherited, and severe optical neuropathy caused by apoptotic degeneration of the retinal ganglion cell layer. Whole-exome sequencing analysis of one PCG family identified two affected siblings who carried a low-frequency homozygous nonsense GUCA1C variant (c.52G > T/p.Glu18Ter/rs143174402). This gene encodes GCAP3, a member of the guanylate cyclase activating protein family, involved in phototransduction and with a potential role in intraocular pressure regulation. Segregation analysis supported the notion that the variant was coinherited with the disease in an autosomal recessive fashion. GCAP3 was detected immunohistochemically in the adult human ocular ciliary epithelium and retina. To evaluate the ocular effect of GUCA1C loss-of-function, a guca1c knockout zebrafish line was generated by CRISPR/Cas9 genome editing. Immunohistochemistry demonstrated the presence of GCAP3 in the non-pigmented ciliary epithelium and retina of adult wild-type fishes. Knockout animals presented up-regulation of the glial fibrillary acidic protein in Müller cells and evidence of retinal ganglion cell apoptosis, indicating the existence of gliosis and glaucoma-like retinal damage. In summary, our data provide evidence for the role of GUCA1C as a candidate gene in PCG and offer new insights into the function of this gene in the ocular anterior segment and the retina. View Full-Text

Keywords: primary congenital glaucoma; exome sequencing; GUCA1C; GCAP3; zebrafish; CRISPR/Cas9

▼ Show Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Supplementary Material

Supplementary File 1:
PDF-Document (PDF, 453 KiB)

Share and Cite

MDPI and ACS Style

Morales-Cámara, S.; Alexandre-Moreno, S.; Bonet-Fernández, J.-M.; Atienzar-Aroca, R.; Aroca-Aguilar, J.-D.; Ferre-Fernández, J.-J.; Méndez, C.-D.; Morales, L.; Fernández-Sánchez, L.; Cuenca, N.; Coca-Prados, M.; Martínez-de-la-Casa, J.-M.; Garcia-Feijoo, J.; Escribano, J. Role of GUCA1C in Primary Congenital Glaucoma and in the Retina: Functional Evaluation in Zebrafish. Genes 2020, 11, 550. https://doi.org/10.3390/genes11050550

AMA Style

Morales-Cámara S, Alexandre-Moreno S, Bonet-Fernández J-M, Atienzar-Aroca R, Aroca-Aguilar J-D, Ferre-Fernández J-J, Méndez C-D, Morales L, Fernández-Sánchez L, Cuenca N, Coca-Prados M, Martínez-de-la-Casa J-M, Garcia-Feijoo J, Escribano J. Role of GUCA1C in Primary Congenital Glaucoma and in the Retina: Functional Evaluation in Zebrafish. Genes. 2020; 11(5):550. https://doi.org/10.3390/genes11050550

Chicago/Turabian Style

Morales-Cámara, Samuel, Susana Alexandre-Moreno, Juan-Manuel Bonet-Fernández, Raquel Atienzar-Aroca, José-Daniel Aroca-Aguilar, Jesús-José Ferre-Fernández, Carmen-Dora Méndez, Laura Morales, Laura Fernández-Sánchez, Nicolas Cuenca, Miguel Coca-Prados, José-María Martínez-de-la-Casa, Julián Garcia-Feijoo, and Julio Escribano. 2020. "Role of GUCA1C in Primary Congenital Glaucoma and in the Retina: Functional Evaluation in Zebrafish" Genes 11, no. 5: 550. https://doi.org/10.3390/genes11050550

Find Other Styles

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Metrics

Abstract views Pdf views Html views

Article Menu

Role of GUCA1C in Primary Congenital Glaucoma and in the Retina: Functional Evaluation in Zebrafish

Abstract

Supplementary Material

Share and Cite

Article Metrics

Article Access Statistics

Article Access Map by Country/Region

Further Information

Guidelines

MDPI Initiatives

Follow MDPI