Soluble Guanylate Cyclase α1-Deficient Mice: A Novel Murine Model for Primary Open Angle Glaucoma

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

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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.

Original languageEnglish
Article numbere60156
JournalPLoS ONE
Volume8
Issue number3
DOIs
StatePublished - 20 Mar 2013
Externally publishedYes

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