Soluble guanylate cyclase α1-deficient mice: a novel murine model for primary open angle glaucoma

• Published in: PloS one Vol. 8; no. 3; p. e60156
• Main Authors: Buys, Emmanuel S, Ko, Yu-Chieh, Alt, Clemens, Hayton, Sarah R, Jones, Alexander, Tainsh, Laurel T, Ren, Ruiyi, Giani, Andrea, Clerté, Maeva, Abernathy, Emma, Tainsh, Robert E T, Oh, Dong-Jin, Malhotra, Rajeev, Arora, Pankaj, de Waard, Nadine, Yu, Binglan, Turcotte, Raphael, Nathan, Daniel, Scherrer-Crosbie, Marielle, Loomis, Stephanie J, 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.03.2013; Public Library of Science (PLoS)
• Subjects: Analysis of Variance; Animal models; Animals; Axons; Biology; Blindness; Cardiology; Collagen; Critical care; Disease Models, Animal; Female; Genetics; Genomes; Glaucoma; Glaucoma, Open-Angle - enzymology; Glaucoma, Open-Angle - physiopathology; Guanylate cyclase; Guanylate Cyclase - deficiency; Guanylate Cyclase - genetics; Hospitals; Immunohistochemistry; Intraocular pressure; Intraocular Pressure - physiology; Medical schools; Medicine; Mice; Mice, Knockout; Mice, Mutant Strains; Mutation; Neuropathy; Nitric oxide; Ophthalmoscopy; Optic nerve; Optic Nerve - pathology; Optic neuropathy; Pain; Pathogenesis; Phenylenediamines; Physicians; Receptors, Cytoplasmic and Nuclear - deficiency; Receptors, Cytoplasmic and Nuclear - genetics; Retina; Retinal Neurons - pathology; Signaling; Soluble Guanylyl Cyclase; Tomography, Optical Coherence; Womens health; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0060156

Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. The molecular signaling involved in the pathogenesis of POAG remains unknown. Here, we report that mice lacking the α1 subunit of the nitric oxide receptor soluble guanylate cyclase represent a novel and translatable animal model of POAG, characterized by thinning of the retinal nerve fiber layer and loss of optic nerve axons in the context of an open iridocorneal angle. The optic neuropathy associated with soluble guanylate cyclase α1-deficiency was accompanied by modestly increased intraocular pressure and retinal vascular dysfunction. Moreover, data from a candidate gene association study suggests that a variant in the locus containing the genes encoding for the α1 and β1 subunits of soluble guanylate cyclase is associated with POAG in patients presenting with initial paracentral vision loss, a disease subtype thought to be associated with vascular dysregulation. These findings provide new insights into the pathogenesis and genetics of POAG and suggest new therapeutic strategies for POAG.