September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Effects of Nitric Oxide Donors on Intraocular Pressure in Cynomolgus Monkeys
Author Affiliations & Notes
  • Shenouda Yacoub
    Novartis Institutes for BioMedical Research, Fort Worth, Texas, United States
  • Byron H Li
    Novartis Institutes for BioMedical Research, Fort Worth, Texas, United States
  • Muneto Mogi
    Novartis Institutes for BioMedical Research, Fort Worth, Texas, United States
  • Dennis S Rice
    Novartis Institutes for BioMedical Research, Fort Worth, Texas, United States
  • Ganesh Prasanna
    Novartis Institutes for BioMedical Research, Fort Worth, Texas, United States
  • Footnotes
    Commercial Relationships   Shenouda Yacoub, Novartis (E); Byron Li, Novartis (E); Muneto Mogi, Novartis (E); Dennis Rice, Novartis (E); Ganesh Prasanna, Novartis (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 6410. doi:
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    • Get Citation

      Shenouda Yacoub, Byron H Li, Muneto Mogi, Dennis S Rice, Ganesh Prasanna; Effects of Nitric Oxide Donors on Intraocular Pressure in Cynomolgus Monkeys. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6410.

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

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Abstract

Purpose : To determine the effects of various nitric oxide (NO) donors on intraocular pressure (IOP) in experimental glaucomatous monkey eyes following topical ocular dosing.

Methods : Chronic ocular hypertension (OHT) was induced in the right eye of cynomolgus monkeys by argon laser trabecular photocoagulation. The effect of various NO donors on IOP was evaluated in conscious animals using a computerized applanation pneumatonometer.

Results : Average baseline IOP in the hypertensive monkey eyes was between 34 - 40 mmHg compared to the 24 – 30 mmHg in the contralateral normotensive eye. A molsidomine derivative: SIN-1 (dosed at 300 mg) caused IOP lowering of 19 ± 3% at 3 hours and 18 ± 4% at 6 hours post-dose in the hypertensive eye. In normotensive monkey eyes, SIN-1 was not efficacious. Isosorbide 5-mononitrate, an isosorbide caused IOP reduction of 14 ± 4% at 1 hour post-dose but was not efficacious at 6 hours post-dose in the hypertensive monkey eye. A dinitroglycerine derivative 1 ,3 Dinitroglycerin (dosed at 50 mg and 500 mg) caused an acute IOP reduction of 14% at 1 hour post-dose for both doses and was minimally efficacious at 6 hours (<8%) for both doses in the hypertensive monkey eye.

Conclusions : NO donors lower IOP in the hypertensive eyes of a monkey model of glaucoma. Among the several classes of NO donors tested, SIN-1 appeared to cause the most robust IOP reduction in the monkey model of glaucoma compared to Isosorbide 5-mononitrate and 1,3-Dinitroglycerin. Additional classes of NO donors are being evaluated for their effects on IOP in this model of glaucoma.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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