Ko, Yu-ChiehHayton, Sarah R.Jones, AlexanderTainsh, Laurel T.Ren, RuiyiGiani, AndreaClerté, MaevaAbernathy, Emmade Waard, NadineTurcotte, RaphaelNathan, DanielLoomis, Stephanie J.Gong, HaiyanBrouckaert, PeterBuys, EmmanuelAlt, ClemensTainsh, RobertOh, Dong-JinMalhotra, RajeevArora, PankajYu, BinglanScherrer-Crosbie, MarielleKang, Jae HeeLin, CharlesRhee, Douglas JWiggs, JaneyGregory-Ksander, MeredithPasquale, LouisBloch, KennethKsander, Bruce2013-05-132013Buys, Emmanuel, Yu-Chieh Ko, Clemens Alt, Sarah R. Hayton, Alexander Jones, Laurel T. Tainsh, Ruiyi Ren, et al. 2013. Soluble guanylate cyclase α1–deficient mice: A novel murine model for primary open angle glaucoma. PLoS ONE 8(3): e60156.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:10622938Primary 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 \(α_1\) 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 \(α_1\)–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 \(α_1\) and \(β_1\) 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.en-USBiologyGeneticsHuman GeneticsGenetic Association StudiesModel OrganismsAnimal ModelsMouseMolecular Cell BiologySignal TransductionSignaling in Cellular ProcessescGMP signalingMedicineCardiovascularPeripheral Vascular DiseasesClinical Research DesignAnimal Models of DiseaseOphthalmologyGlaucomaRetinal DisordersJournal Article2013-05-1310.1371/journal.pone.0060156