Soluble guanylate cyclase ?1-deficient mice: a novel murine model for primary open angle glaucoma.
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ABSTRACT:
SUBMITTER: Buys ES
PROVIDER: S-EPMC3603933 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
Publications
Soluble guanylate cyclase α1-deficient mice: a novel murine model for primary open angle glaucoma.
Buys Emmanuel S ES Ko Yu-Chieh YC Alt Clemens C Hayton Sarah R SR Jones Alexander A Tainsh Laurel T LT Ren Ruiyi R Giani Andrea A Clerté Maeva M Abernathy Emma E Tainsh Robert E T RE Oh Dong-Jin DJ Malhotra Rajeev R Arora Pankaj P de Waard Nadine N Yu Binglan B Turcotte Raphael R Nathan Daniel D Scherrer-Crosbie Marielle M Loomis Stephanie J SJ Kang Jae H JH Lin Charles P CP Gong Haiyan H Rhee Douglas J DJ Brouckaert Peter P Wiggs Janey L JL Gregory Meredith S MS Pasquale Louis R LR Bloch Kenneth D KD Ksander Bruce R BR
PloS one 20130320 3
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 gua ...[more]
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2022-11-11 | GSE217514 | GEO
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2008-06-12 | E-GEOD-2387 | biostudies-arrayexpress
Project description:The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays a key role in the pathogenesis of pulmonary hypertension (PH). Targeted treatments include phosphodiesterase type 5 inhibitors (PDE5i) and sGC stimulators. The sGC stimulator riociguat is approved for the treatment of pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). sGC stimulators have a dual mechanism of action, enhancing the sGC response to endogenous NO and directly stimulating sGC, independent of NO. This increase in cGMP production via a dual mechanism differs from PDE5i, which protects cGMP from degradation by PDE5, rather than increasing its production. sGC stimulators may therefore have the potential to increase cGMP levels under conditions of NO depletion that could limit the effectiveness of PDE5i. Such differences in mode of action between sGC stimulators and PDE5i could lead to differences in treatment efficacy between the classes. In addition to vascular effects, sGC stimulators have the potential to reduce inflammation, angiogenesis, fibrosis and right ventricular hypertrophy and remodelling. In this review we describe the evolution of treatments targeting the NO-sGC-cGMP pathway, with a focus on PH.
| S-EPMC10957071 | biostudies-literature
Project description:PURPOSE:This study sought to investigate the role of rare copy number variation (CNV) in age-related disorders of blindness, with a focus on primary open-angle glaucoma (POAG). Data are reported from a whole-genome copy number screen in a large cohort of 400 individuals with POAG and 500 age-matched glaucoma-free subjects. METHODS:DNA samples from patients and controls were tested for CNVs using a combination of two microarray platforms. The signal intensity data generated from these arrays were then analyzed with multiple CNV detection programs including CNAG version 2.0, PennCNV, and dChip. RESULTS:A total of 11 validated CNVs were identified as recurrent in the POAG set and absent in the age-matched control set. This set included CNVs on 5q23.1 (DMXL1, DTWD2), 20p12 (PAK7), 12q14 (C12orf56, XPOT, TBK1, and RASSF3), 12p13.33 (TULP3), and 10q34.21 (PAX2), among others. The CNVs presented here are exceedingly rare and are not found in the Database of Genomic Variants. Moreover, expression data from ocular tissue support the role of these CNV-implicated genes in vision-related processes. In addition, CNV locations of DMXL1 and PAK7 overlap previously identified linkage signals for glaucoma on 5p23.1 and 20p12, respectively. CONCLUSIONS:The data are consistent with the hypothesis that rare CNV plays a role in the development of POAG.
| S-EPMC3207715 | biostudies-literature
Project description:Purpose of review:Individuals of African descent are at highest risk for developing primary open-angle glaucoma (POAG), a devastating disease and major contributor of blindness worldwide. Currently, there is a large dearth of knowledge in this area despite a critical need for better understanding the underlying genetic and environmental factors afflicting this population. Here we highlight the current literature exploring the genetics of POAG in African Americans. Recent findings:Current studies have yet to replicate European POAG index variants (i.e. CDKN2B-AS1 and SIX1/SIX6) in African Americans or to definitely exclude that these loci contribute to risk in African descent populations. Recent studies have evaluated clinical features that may account for some differences in POAG risk between African Americans and European Americans. Summary:In summary, little headway has been made in elucidating the genetics of primary open-angle glaucoma in African Americans and other individuals of African descent.
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