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The ability of nitric oxide to lower intraocular pressure is dependent on guanylyl cyclase

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Abstract
PURPOSE. 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. METHODS. IOP and aqueous humor (AqH) outflow were measured in WT and GC-1 alpha subunit null (GC-1-/-) mice. Mice breathed 40 parts per million (ppm) NO in O-2 or control gas (N-2/O-2). 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. RESULTS. 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.% 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. CONCLUSIONS. Breathing NO reduced IOP and increased outflow facility in a GC-dependent manner in mice. Exposure of ovine eyes to NO lowers IOP.
Keywords
OPEN-ANGLE GLAUCOMA, HUMOR OUTFLOW FACILITY, LATANOPROSTENE BUNOD, TRABECULAR MESHWORK, PULMONARY-HYPERTENSION, HYDROGEN-SULFIDE, OCULAR, HYPERTENSION, PRECLINICAL MODELS, COMMON VARIANTS, KNOCKOUT MICE, intraocular pressure, nitric oxide, soluble guanylyl cyclase

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MLA
Muenster, Stefan et al. “The Ability of Nitric Oxide to Lower Intraocular Pressure Is Dependent on Guanylyl Cyclase.” INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 58.11 (2017): 4826–4835. Print.
APA
Muenster, S., Lieb, W. S., Fabry, G., Allen, K. N., Kamat, S. S., Guy, A. H., Dordea, A. C., et al. (2017). The ability of nitric oxide to lower intraocular pressure is dependent on guanylyl cyclase. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 58(11), 4826–4835.
Chicago author-date
Muenster, Stefan, Wolfgang S Lieb, Gregor Fabry, Kaitlin N Allen, Shivani S Kamat, Ann H Guy, Ana C Dordea, et al. 2017. “The Ability of Nitric Oxide to Lower Intraocular Pressure Is Dependent on Guanylyl Cyclase.” Investigative Ophthalmology & Visual Science 58 (11): 4826–4835.
Chicago author-date (all authors)
Muenster, Stefan, Wolfgang S Lieb, Gregor Fabry, Kaitlin N Allen, Shivani S Kamat, Ann H Guy, Ana C Dordea, Leandro Teixeira, Robert E Tainsh, Binglan Yu, Wei Zhu, Nicole E Ashpole, Rajeev Malhotra, Peter Brouckaert, Donald B Bloch, Marielle Scherrer-Crosbie, W Daniel Stamer, Markus H Kuehn, Louis R Pasquale, and Emmanuel S Buys. 2017. “The Ability of Nitric Oxide to Lower Intraocular Pressure Is Dependent on Guanylyl Cyclase.” Investigative Ophthalmology & Visual Science 58 (11): 4826–4835.
Vancouver
1.
Muenster S, Lieb WS, Fabry G, Allen KN, Kamat SS, Guy AH, et al. The ability of nitric oxide to lower intraocular pressure is dependent on guanylyl cyclase. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE. 2017;58(11):4826–35.
IEEE
[1]
S. Muenster et al., “The ability of nitric oxide to lower intraocular pressure is dependent on guanylyl cyclase,” INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, vol. 58, no. 11, pp. 4826–4835, 2017.
@article{8538836,
  abstract     = {PURPOSE. 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. 
METHODS. IOP and aqueous humor (AqH) outflow were measured in WT and GC-1 alpha subunit null (GC-1-/-) mice. Mice breathed 40 parts per million (ppm) NO in O-2 or control gas (N-2/O-2). 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. 
RESULTS. 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.% 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. 
CONCLUSIONS. Breathing NO reduced IOP and increased outflow facility in a GC-dependent manner in mice. Exposure of ovine eyes to NO lowers IOP.},
  author       = {Muenster, Stefan and Lieb, Wolfgang S and Fabry, Gregor and Allen, Kaitlin N and Kamat, Shivani S and Guy, Ann H and Dordea, Ana C and Teixeira, Leandro and Tainsh, Robert E and Yu, Binglan and Zhu, Wei and Ashpole, Nicole E and Malhotra, Rajeev and Brouckaert, Peter and Bloch, Donald B and Scherrer-Crosbie, Marielle and Stamer, W Daniel and Kuehn, Markus H and Pasquale, Louis R and Buys, Emmanuel S},
  issn         = {0146-0404},
  journal      = {INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE},
  keywords     = {OPEN-ANGLE GLAUCOMA,HUMOR OUTFLOW FACILITY,LATANOPROSTENE BUNOD,TRABECULAR MESHWORK,PULMONARY-HYPERTENSION,HYDROGEN-SULFIDE,OCULAR,HYPERTENSION,PRECLINICAL MODELS,COMMON VARIANTS,KNOCKOUT MICE,intraocular pressure,nitric oxide,soluble guanylyl cyclase},
  language     = {eng},
  number       = {11},
  pages        = {4826--4835},
  title        = {The ability of nitric oxide to lower intraocular pressure is dependent on guanylyl cyclase},
  url          = {http://dx.doi.org/10.1167/iovs.17-22168},
  volume       = {58},
  year         = {2017},
}

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