June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Inhaled Nitric Oxide: an sGC-dependent IOP lowering agent
Author Affiliations & Notes
  • Wolfgang-Sebastian Lieb
    Anesthesia, Critical Care and Pain Medicine, Mass General Hospital, Wildberg, Germany
  • Stefan Munster
    Anesthesia, Critical Care and Pain Medicine, Mass General Hospital, Wildberg, Germany
  • Ana Dordea
    Anesthesia, Critical Care and Pain Medicine, Mass General Hospital, Wildberg, Germany
  • Sara Vandenwijngaert
    Anesthesia, Critical Care and Pain Medicine, Mass General Hospital, Wildberg, Germany
  • Robert Tainsh
    Anesthesia, Critical Care and Pain Medicine, Mass General Hospital, Wildberg, Germany
  • Warren Myron Zapol
    Anesthesia, Critical Care and Pain Medicine, Mass General Hospital, Wildberg, Germany
  • Emmanuel S Buys
    Anesthesia, Critical Care and Pain Medicine, Mass General Hospital, Wildberg, Germany
  • Footnotes
    Commercial Relationships Wolfgang-Sebastian Lieb, None; Stefan Munster, None; Ana Dordea, None; Sara Vandenwijngaert, None; Robert Tainsh, None; Warren Zapol, None; Emmanuel Buys, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4854. doi:
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      Wolfgang-Sebastian Lieb, Stefan Munster, Ana Dordea, Sara Vandenwijngaert, Robert Tainsh, Warren Myron Zapol, Emmanuel S Buys; Inhaled Nitric Oxide: an sGC-dependent IOP lowering agent . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4854.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract
 
Purpose
 

The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway regulates intraocular pressure (IOP). Preclinical and clincial studies have demonstrated the ability of NO-donor compounds to lower IOP (e.g. VESNEO®). The use of inhaled NO gas (iNO), a specific pulmonary but not systemic vasodilator, is an approved therapy for pulmonary hypertension and is under development as a treatment for other cardiovascular diseases (e.g. for myocardial Ischemia, the NOMI trial). We hypothesized that breathing NO lowers IOP in an sGC-dependent manner.

 
Methods
 

Anesthetized IOP model: 10- to 20-week-old male wild type (WT) mice and mice deficient in the a1 subunit of sGC (sGCa1-/- mice; n=9, each) were anesthetized with isoflurane using a standard protocol resulting in a stable IOP baseline. Ten minutes after baseline measurement, IOP was measured again in mice breathing 1.8 % isoflurane and either control gas (N2 balanced in O2) or 40 ppm NO balanced in O2. Awake IOP model: WT mice were acclimated to awake IOP measurements (every other day for 2 weeks). 40 min after baseline measurements, IOP was measured in mice breathing either control gas or 40 ppm iNO (n=8, each) in an incubation chamber.

 
Results
 

Breathing control gas did not affect IOP in WT or sGCa1-/- mice (Figure 1). Breathing iNO decreased IOP in both anesthetized WT mice (9.860.31 vs 8.420.51 mmHg at baseline and after iNO, respectively, Figure 1A) and awake WT mice (14.131.95 vs 10.931.01 mmHg, at baseline and after 40 min iNO, respectively, Figure 1B). In contrast, iNO did not lower IOP in sGCa1-/- mice (9.750.31 vs 9.460.30 mmHg at baseline and after iNO, respectively, Figure 1A).

 
Conclusions
 

Inhalation of 40 ppm iNO decreased IOP in anesthetized and awake WT mice but not in sGCa1-/- mice. These findings confirm that NO is an IOP-lowering agent and identify NO-gas as a possible therapeutic approach to acutely lower IOP. In addition, our results identify sGC as the downstream target of NO’s ability to lower IOP. sGC stimulators, under development for treatment of cardiovascular diseases, such as the recently approved ADEMPAS®, may be considered as a novel treatment option for elevated IOP.  

 
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