RT Journal Article
T1 Role of GUCA1C in Primary Congenital Glaucoma and in the Retina: Functional Evaluation in Zebrafish
A1 Morales Cámara, Samuel
A1 Alexandre Moreno, Susana
A1 Bonet Fernández, Juan Manuel
A1 Atienzar Aroca, Raquel
A1 Aroca Aguilar, José Daniel
A1 Ferre Fernández, Jesús José
A1 Méndez Hernández, Carmen D.
A1 Morales Fernández, Laura
A1 Fernández Sánchez, Laura
A1 Cuenca Navarro, Nicolás
A1 Coca Prados, Miguel
A1 Martínez de la Casa, Jose Maria
A1 García Feijoo, Julián
A1 Escribano, Julio
AB 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.
YR 2020
FD 2020-03-29
LK https://hdl.handle.net/20.500.14352/6162
UL https://hdl.handle.net/20.500.14352/6162
LA eng
NO Version 1 : Received: 27 March 2020 / Approved: 29 March 2020 / Online: 29 March 2020
NO Instituto de Salud Carlos III/FEDER
NO Junta de Comunidades de Castilla La Mancha
DS Docta Complutense
RD 16 may 2024