ArticleThe Journal of biological chemistry2011
Regulation of anterior chamber drainage by bicarbonate-sensitive soluble adenylyl cyclase in the ciliary body.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci.Nature communications · 2018Pooled it
- Targeting Soluble Adenylyl Cyclase for On-Demand Contraception.Physiology (Bethesda, Md.) · 2026Review
- Review
- Carbonic Anhydrase Inhibitor Modulation of Intraocular Pressure Is Independent of Soluble Adenylyl Cyclase.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2023Article
- Scaffold Hopping and Optimization of Small Molecule Soluble Adenyl Cyclase Inhibitors Led by Free Energy Perturbation.Journal of chemical information and modeling · 2023Article
- Design, Synthesis, and Pharmacological Evaluation of Second-Generation Soluble Adenylyl Cyclase (sAC, ADCY10) Inhibitors with Slow Dissociation Rates.Journal of medicinal chemistry · 2022Article
- Quantitative analysis of exosomes in the aqueous humor of Korean patients with pseudoexfoliation glaucoma.Scientific reports · 2022Article
- Assessing potency and binding kinetics of soluble adenylyl cyclase (sAC) inhibitors to maximize therapeutic potential.Frontiers in physiology · 2022Article
- Strategies to safely target widely expressed soluble adenylyl cyclase for contraception.Frontiers in pharmacology · 2022Article
- Bicarbonate, carbon dioxide and pH sensing via mammalian bicarbonate-regulated soluble adenylyl cyclase.Interface focus · 2021Review
- Optimization of lead compounds into on-demand, nonhormonal contraceptives: leveraging a public-private drug discovery institute collaboration†.Biology of reproduction · 2020Article
- Pharmacological modulation of the COPharmacology & therapeutics · 2018Review
- Functional Significance of the Adcy10-Dependent Intracellular cAMP Compartments.Journal of cardiovascular development and disease · 2018Review
- Differential Intraocular Pressure Measurements by Tonometry and Direct Cannulation After Treatment with Soluble Adenylyl Cyclase Inhibitors.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2017Article
- Model systems for the study of steroid-induced IOP elevation.Experimental eye research · 2017Review
- Unconventional aqueous humor outflow: A review.Experimental eye research · 2017Review
- Role of cyclic AMP in the eye with glaucoma.BMB reports · 2017Review
- Discovery of LRE1 as a specific and allosteric inhibitor of soluble adenylyl cyclase.Nature chemical biology · 2016Article
- Bithionol Potently Inhibits Human Soluble Adenylyl Cyclase through Binding to the Allosteric Activator Site.The Journal of biological chemistry · 2016Article
- Physical Factors Affecting Outflow Facility Measurements in Mice.Investigative ophthalmology & visual science · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Glaucoma is a leading cause of blindness affecting as many as 2.2 million Americans. All current glaucoma treatment strategies aim to reduce intraocular pressure (IOP). IOP results from the resistance to drainage of aqueous humor (AH) produced by the ciliary body in a process requiring bicarbonate. Once secreted into the anterior chamber, AH drains from the eye via two pathways: uveoscleral and pressure-dependent or conventional outflow (C(t)). Modulation of "inflow" and "outflow" pathways is thought to occur via distinct, local mechanisms. Mice deficient in the bicarbonate channel bestrophin-2 (Best2), however, exhibit a lower IOP despite an increase in AH production. Best2 is expressed uniquely in nonpigmented ciliary epithelial (NPE) cells providing evidence for a bicarbonate-dependent communicative pathway linking inflow and outflow. Here, we show that bicarbonate-sensitive soluble adenylyl cyclase (sAC) is highly expressed in the ciliary body in NPE cells, but appears to be absent from drainage tissues. Pharmacologic inhibition of sAC in mice causes a significant increase in IOP due to a decrease in C(t) with no effect on inflow. In mice deficient in sAC IOP is elevated, and C(t) is decreased relative to wild-type mice. Pharmacologic inhibition of sAC did not alter IOP or C(t) in sAC-deficient mice. Based on these data we propose that the ciliary body can regulate C(t) and that sAC serves as a critical sensor of bicarbonate in the ciliary body regulating the secretion of substances into the AH that govern outflow facility independent of pressure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.