title: Soluble guanylate cyclase α1-deficient mice: a novel murine model for primary open angle glaucoma.
abstract: 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.
authors.affiliation: Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States of America. Ebuys@partners.org
authors.forename: Emmanuel S
authors.initials: ES
authors.lastname: Buys
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Ko
authors.forename: Clemens
authors.initials: C
authors.lastname: Alt
authors.forename: Sarah R
authors.initials: SR
authors.lastname: Hayton
authors.forename: Alexander
authors.initials: A
authors.lastname: Jones
authors.forename: Laurel T
authors.initials: LT
authors.lastname: Tainsh
authors.forename: Ruiyi
authors.initials: R
authors.lastname: Ren
authors.forename: Andrea
authors.initials: A
authors.lastname: Giani
authors.forename: Maeva
authors.initials: M
authors.lastname: Clerté
authors.forename: Emma
authors.initials: E
authors.lastname: Abernathy
authors.forename: Robert E T
authors.initials: RE
authors.lastname: Tainsh
authors.forename: Dong-Jin
authors.initials: DJ
authors.lastname: Oh
authors.forename: Rajeev
authors.initials: R
authors.lastname: Malhotra
authors.forename: Pankaj
authors.initials: P
authors.lastname: Arora
authors.forename: Nadine
authors.initials: N
authors.lastname: de Waard
authors.forename: Binglan
authors.initials: B
authors.lastname: Yu
authors.forename: Raphael
authors.initials: R
authors.lastname: Turcotte
authors.forename: Daniel
authors.initials: D
authors.lastname: Nathan
authors.forename: Marielle
authors.initials: M
authors.lastname: Scherrer-Crosbie
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Loomis
authors.forename: Jae H
authors.initials: JH
authors.lastname: Kang
authors.forename: Charles P
authors.initials: CP
authors.lastname: Lin
authors.forename: Haiyan
authors.initials: H
authors.lastname: Gong
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Rhee
authors.forename: Peter
authors.initials: P
authors.lastname: Brouckaert
authors.forename: Janey L
authors.initials: JL
authors.lastname: Wiggs
authors.forename: Meredith S
authors.initials: MS
authors.lastname: Gregory
authors.forename: Louis R
authors.initials: LR
authors.lastname: Pasquale
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bloch
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Ksander
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005902:Glaucoma, Open-Angle / Q000201:enzymology* / Q000503:physiopathology*; D006162:Guanylate Cyclase / Q000172:deficiency* / Q000235:genetics; D007150:Immunohistochemistry; D007429:Intraocular Pressure / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009887:Ophthalmoscopy; D009900:Optic Nerve / Q000473:pathology*; D010655:Phenylenediamines; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency* / Q000235:genetics; D055351:Retinal Neurons / Q000473:pathology*; D000071756:Soluble Guanylyl Cyclase; D041623:Tomography, Optical Coherence
chemical_list: D010655:Phenylenediamines; D018160:Receptors, Cytoplasmic and Nuclear; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; C029728:4-phenylenediamine