Enhanced Oxygen Saturation in Optic Nerve Head of Non-Human Primate Eyes Following the Intravitreal Injection of NCX 434, an Innovative Nitric Oxide-Donating Glucocorticoid
- 1 April 2011
- journal article
- research article
- Published by Mary Ann Liebert Inc in Journal of Ocular Pharmacology and Therapeutics
- Vol. 27 (2), 115-121
- https://doi.org/10.1089/jop.2010.0150
Abstract
Purpose: Hypoxia of the retina and optic nerve head (ONH) is believed to be pivotal in the development of ocular vascular disorders, including diabetic macular edema (DME). Glucocorticoids are among the most effective agents for the treatment of back of the eye diseases. However, this class of compounds is highly liable to increase intraocular pressure (IOP) and does not improve ocular perfusion or tissue oxygenation. Nitric oxide (NO) has vasodilating properties and lowers IOP in experimental models and humans, suggesting that its properties might complement those of glucocorticoids. NCX 434 is an NO-donating triamcinolone acetonide (TA) that is less likely to increase IOP while targeting both the vascular and inflammatory components of DME. Methods: NCX 434 was studied in vitro with respect to its NO-releasing properties in isolated methoxamine-precontracted rabbit aortic rings and glucocorticoid-like activity in recombinant human glucocorticoid receptors. IOP and oxygen saturation in the ONH and overlaying arteries and veins were studied in the anesthetized cynomolgus monkey. Measurements were taken using, respectively, an applanation tonometer and a hyperspectral imaging system before and 7, 14, 21, 31 and 41 days after the intravitreal injection of NCX 434 (5.8 mg/eye) or TA equimolar doses (4.0 mg/eye). Results: NCX 434 inhibited 3H-dexamethasone-specific binding (IC50=34±5 nM) on human glucocorticoid receptors and elicited NO-dependent aortic ring relaxation (EC50 of 0.5±0.1 μM, Emax 98.9%). In monkey eyes, NCX 434 enhanced, whereas TA did not, oxygen saturation in various ONH areas (*PIOP=+3.31±0.51 mmHg, 30.8%, over baseline, NS). Conclusions: NCX 434 enhances ocular tissue oxygenation. This feature appears to depend on its NO-donating properties; thus, the compound deserves to be further investigated for the treatment of DME and other ocular disorders with impaired ocular perfusion.Keywords
This publication has 30 references indexed in Scilit:
- A Novel Nitric Oxide Releasing Prostaglandin Analog, NCX 125, Reduces Intraocular Pressure in Rabbit, Dog, and Primate Models of GlaucomaJournal of Ocular Pharmacology and Therapeutics, 2010
- Interactions Between Hyperglycemia and HypoxiaDiabetes, 2004
- Nitric oxide proxies and ocular perfusion pressure in primary open angle glaucomaBritish Journal of Ophthalmology, 2004
- Hyperspectral Imaging for Measurement of Oxygen Saturation in the Optic Nerve HeadInvestigative Ophthalmology & Visual Science, 2004
- Supplemental Oxygen Improves Diabetic Macular Edema: A Pilot StudyPublished by Association for Research in Vision and Ophthalmology (ARVO) ,2004
- A simple algorithm forin vivoocular fundus oximetry compensating for non-haemoglobin absorption and scatteringPhysics in Medicine & Biology, 2002
- In vivo measurement of the oxygen saturation of retinal vessels in healthy volunteersIEEE Transactions on Biomedical Engineering, 1999
- The effect of isosorbide-mononitrate eye drops on the human intraocular pressure and aqueous humor dynamicsInternational Ophthalmology, 1991
- Nitric oxide: physiology, pathophysiology, and pharmacology.1991
- Saline infusion into lumen of resistance artery and small vein causes contractionAmerican Journal of Physiology-Heart and Circulatory Physiology, 1990