Soluble Guanylate Cyclase a1–Deficient Mice: A Novel Murine Model for Primary Open Angle Glaucoma

Buys, Emmanuel; Ko, Yu-Chieh; Alt, Clemens; Hayton, Sarah; Jones, Alexander; Tainsh, Laurel T.; Ren, Ruiyi; Giani, Andrea; Clerté, Maëva; Abernathy, Emma; Tainsh, Robert E.; Oh, Dong-Jin; Malhotra, Rajeev; Arora, Pankaj; Waard, Nadine de; Yu, Binglan; Turcotte, Raphaël; Nathan, Daniel I.; Scherrer‐Crosbie, Marielle; Loomis, Stephanie; Kang, Jae H.; Lin, Charles P.; Gong, Haiyan; Rhee, Douglas J.; Brouckaert, Peter; Wiggs, Janey L.; Gregory, Meredith S.; Pasquale, Louis R.; Bloch, Kenneth D.; Ksander, Bruce R.

doi:10.5214/ans.0972.7531.200207

Cited by 3 publications

(2 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Because of this property, guanylate cyclase activators have been proposed as therapeutic agents for glaucoma [26,27]. In addition, it has been reported that a KO mouse for the α-1 subunit of soluble guanylate cyclase developed glaucoma [36]. Based on these data, we hypothesize that the loss of GUCA1C function could result in decreased cGMP, increased IOP, and glaucoma.…”

Section: Discussionmentioning

confidence: 78%

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

Morales-Cámara

Alexandre-Moreno

Bonet-Fernández

et al. 2020

Genes

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 78%

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

Morales-Cámara

Alexandre-Moreno

Bonet-Fernández

et al. 2020

Genes

View full text Add to dashboard Cite

show abstract

“…Because of this property, guanylate cyclase activators have been proposed as therapeutic agents for glaucoma [32,33]. In addition, it has been reported that a KO mouse for the alpha-1 subunit of soluble guanylate cyclase developed glaucoma [34]. Based on these data, we hypothesize that the loss of GUCA1C function could result in decreased cGMP, increased IOP, and glaucoma.…”

Section: Discussionmentioning

confidence: 79%

Role of <em>GUCA1C </em>in Primary Congenital Glaucoma and in the Retina: Functional Evaluation in Zebrafish

Morales-Cámara¹,

Alexandre-Moreno²,

Bonet-Fernández³

et al. 2020

Preprint

View full text Add to dashboard Cite

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.

show abstract

NCX 470 Reduces Intraocular Pressure More Effectively Than Lumigan in Dogs and Enhances Conventional and Uveoscleral Outflow in Non-Human Primates and Human Trabecular Meshwork/Schlemm's Canal Constructs

Galli,

Bastia,

Hubatsch

et al. 2024

Journal of Ocular Pharmacology and Therapeutics

View full text Add to dashboard Cite

Soluble Guanylate Cyclase a1–Deficient Mice: A Novel Murine Model for Primary Open Angle Glaucoma

Cited by 3 publications

References 3 publications

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

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

Role of <em>GUCA1C </em>in Primary Congenital Glaucoma and in the Retina: Functional Evaluation in Zebrafish

NCX 470 Reduces Intraocular Pressure More Effectively Than Lumigan in Dogs and Enhances Conventional and Uveoscleral Outflow in Non-Human Primates and Human Trabecular Meshwork/Schlemm's Canal Constructs

Contact Info

Product

Resources

About