Journal article
The Ability of Nitric Oxide to Lower Intraocular Pressure Is Dependent on Guanylyl Cyclase
Investigative ophthalmology & visual science, Vol.58(11), pp.4826-4835
09/01/2017
DOI: 10.1167/iovs.17-22168
PMCID: PMC5624778
PMID: 28973329
Abstract
While nitric oxide (NO) donors are emerging as treatments for glaucoma, the mechanism by which NO lowers intraocular pressure (IOP) is unclear. NO activates the enzyme guanylyl cyclase (GC) to produce cyclic guanosine monophosphate. We studied the ocular effects of inhaled and topically applied NO gas in mice and lambs, respectively. IOP and aqueous humor (AqH) outflow were measured in WT and GC-1α subunit null (GC-1-/-) mice. Mice breathed 40 parts per million (ppm) NO in O2 or control gas (N2/O2). We also studied the effect of ocular NO gas exposure (80, 250, 500, and 1000 ppm) on IOP in anesthetized lambs. NO metabolites were measured in AqH and plasma. In awake WT mice, breathing NO for 40 minutes lowered IOP from 14.4 ± 1.9 mm Hg to 10.9 ± 1.0 mm Hg (n = 11, P < 0.001). Comparable results were obtained in anesthetized WT mice (n = 10, P < 0.001). In awake or anesthetized GC-1-/- mice, IOP did not change under similar experimental conditions (P ≥ 0.08, n = 20). Breathing NO increased in vivo outflow facility in WT but not GC-1-/- mice (+13.7 ± 14.6% vs. -12.1 ± 9.4%, n = 4 each, P < 0.05). In lambs, ocular exposure to NO lowered IOP in a dose-dependent manner (-0.43 mm Hg/ppm NO; n = 5 with 40 total measurements; P = 0.04) without producing corneal pathology or altering pulmonary and systemic hemodynamics. After ocular NO exposure, NO metabolites were increased in AqH (n = 8, P < 0.001) but not in plasma. Breathing NO reduced IOP and increased outflow facility in a GC-dependent manner in mice. Exposure of ovine eyes to NO lowers IOP.
Details
- Title: Subtitle
- The Ability of Nitric Oxide to Lower Intraocular Pressure Is Dependent on Guanylyl Cyclase
- Creators
- Stefan Muenster - Department of Anesthesiology and Critical Care Medicine, University Hospital Bonn, Bonn, GermanyWolfgang S Lieb - Institute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, GermanyGregor Fabry - Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, Massachusetts, United StatesKaitlin N Allen - Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, Massachusetts, United StatesShivani S Kamat - Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United StatesAnn H Guy - Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United StatesAna C Dordea - Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, Massachusetts, United StatesLeandro Teixeira - Department of Pathological Science, School of Veterinary Medicine, University of Wisconsin, Wisconsin, United StatesRobert E Tainsh - Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, Massachusetts, United StatesBinglan Yu - Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, Massachusetts, United StatesWei Zhu - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United StatesNicole E Ashpole - Department of Biomedical Engineering, Duke University, Durham, North Carolina, United StatesRajeev Malhotra - Cardiovascular Research Center and Cardiology Division of the Department of Medicine, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, Massachusetts, United StatesPeter Brouckaert - Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium Department of Molecular Biomedical Research, VIB, Ghent, BelgiumDonald B Bloch - The Center for Immunology and Inflammatory Diseases and the Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, Massachusetts, United StatesMarielle Scherrer-Crosbie - Cardiac Ultrasound Laboratory and Division of Cardiology, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, Massachusetts, United StatesW Daniel Stamer - Department of Biomedical Engineering, Duke University, Durham, North Carolina, United StatesMarkus H Kuehn - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United StatesLouis R Pasquale - Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United StatesEmmanuel S Buys - Anesthesia Center for Critical Care Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital Research Institute and Harvard Medical School, Boston, Massachusetts, United States
- Resource Type
- Journal article
- Publication Details
- Investigative ophthalmology & visual science, Vol.58(11), pp.4826-4835
- DOI
- 10.1167/iovs.17-22168
- PMID
- 28973329
- PMCID
- PMC5624778
- NLM abbreviation
- Invest Ophthalmol Vis Sci
- ISSN
- 0146-0404
- eISSN
- 1552-5783
- Publisher
- United States
- Grant note
- R01 EY022359 / NEI NIH HHS R01 DK082971 / NIDDK NIH HHS I01 RX001163 / RRD VA R01 EY022746 / NEI NIH HHS P30 EY005722 / NEI NIH HHS I50 RX003002 / RRD VA
- Language
- English
- Date published
- 09/01/2017
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9983980056402771
Metrics
33 Record Views