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Contents:
  1. Nitric oxide in the eye: multifaceted roles and diverse outcomes.
  2. Register for a free account
  3. How Nitric Oxide Works in the Body
  4. Online Topics: Nitric Oxide in Glaucoma

In a rat optic nerve crush model, 0. In vitro studies in cultured retinal neuronal cells have demonstrated that NO can have either neuroprotective or neurodegenerative properties depending on the dose.

Nitric oxide in the eye: multifaceted roles and diverse outcomes.

Nipradilol was neuroprotective against oxidative stress-induced cell death in RGCs and mediated S-nitrosylation of Kelch-like ECH-associated protein Keap1 , which regulates the transcriptional activation of the antioxidant protein heme oxygenase In the case of topical NO therapy, data is lacking; however, studies using nipradilol demonstrate that this particular NO donor reaches the retina at levels that can mediate neuroprotective effects. The retinal, ONH, and choroidal endothelium play a key role in maintaining the homeostasis of vascular tone and regulation of blood flow by releasing vasoactive mediators including NO.

This is in accordance with the hypothesis of local alteration of the NO signaling pathway at the level of the ocular vasculature in glaucoma. In glaucoma patients, while iNOS and nNOS upregulation in the ONH may contribute to the oxidative stress resulting from repeated ischemia-reperfusion injury, elevated eNOS in vascular endothelia may be neuroprotective through causing vasodilation and increased ONH blood flow. A number of studies support the vasodilatory role of NO on ocular blood vessels. For example, in isolated bovine retinal and ciliary arteries SNP elicits relaxation.

Similarly, a clinical study demonstrated that intravenously administered nitroglycerin, ISDN, and SNP decreased vascular resistance but did not affect ocular hemodynamics, thought to be due to a reduction in blood pressure. Overall, the literature on NO and ocular blood flow suggest that NO plays a major role in controlling basal ocular vascular tone and that exogenous NO delivery can modulate ocular blood flow, with effects dependent on numerous factors including the specific NO donor used, its route of administration and the ocular vascular region studied.

Other mechanisms such as reduction in AHF and modulation of uveoscleral outflow may also play a role. Nitric oxide could also exert additional positive effects on cell health and survival in ocular tissues. Physiologic low concentrations of NO provide cell sparing activities because of its antiinflammatory and antiapoptotic properties. An important consideration for exogenous NO delivery as a glaucoma therapy appears to be dosing.

As is the case for many drugs or biological effectors, the biphasic nature of NO releasing agents in numerous cellular responses is well known. Despite the availability of various treatments to reduce elevated IOP, the most commonly prescribed glaucoma drugs do not target the compromised function of the trabecular outflow pathway. Therapeutic use of NO has the potential to benefit glaucoma patients by reducing IOP via targeting the diseased conventional outflow pathway. The information presented on latanoprostene bunod concerns a use that has not been approved by the US Food and Drug Administration.


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Disclosure: M. Impagnatiello , Nicox E ; E. Ongini , Nicox E ; E. Bastia , Nicox E. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.


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Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Pharmacol Rev. Boo YC Jo H. Flow-dependent regulation of endothelial nitric oxide synthase: role of protein kinases. Am J Physiol Cell Physiol.

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Handy DE Loscalzo J. Nitric oxide and posttranslational modification of the vascular proteome: S-nitrosation of reactive thiols. Arterioscler Thromb Vasc Biol. Colasanti M Suzuki H.

What is Nitric Oxide (NO) and how it works in your body

The dual personality of NO. Trends Pharmacol Sci. Nat Cell Biol. Nitric oxide in the eye: multifaceted roles and diverse outcomes. Surv Ophthalmol. Nitric oxide and peroxynitrite in health and disease. Physiol Rev. Nitric oxide: a review of its role in retinal function and disease. Vision Res. Discovery of the nitric oxide signaling pathway and targets for drug development. Front Biosci. The emerging multifaceted roles of nitric oxide. Ann Surg.

How Nitric Oxide Works in the Body

Moncada S. Nitric oxide in the vasculature: physiology and pathophysiology. Ann N Y Acad Sci. Physiological and pathophysiological roles of nitric oxide. Free Rad Biol Med. Toda N Nakanishi-Toda M. Nitric oxide: ocular blood flow, glaucoma, and diabetic retinopathy. Prog Retin Eye Res.

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Sommer A. Intraocular pressure and glaucoma. Am J Ophthalmol. Arch Ophthalmol.

Online Topics: Nitric Oxide in Glaucoma

PLoS One. Alm A Nilsson SF. Uveoscleral outflow—a review. Exp Eye Res. Endogenous bioactive lipids and the regulation of conventional outflow facility. Expert Rev Ophthalmol. Identification of an extensive system of nitric oxide-producing cells in the ciliary muscle and outflow pathway of the human eye. Histochemical study on rat tear film and ocular surface epithelial cells. Curr Eye Res.

NADPH diaphorase localization and nitric oxide synthetase activity in the retina and anterior uvea of the rabbit eye. Brain Res.

phaetweenilco.gq Elevation of nitric oxide production in human trabecular meshwork by increased pressure. Graefes Arch Clin Exp Ophthalmol. Nitric oxide production by isolated human and porcine ciliary processes. Relaxation of trabecular meshwork and ciliary muscle by release of nitric oxide.

Effect of nitric oxide compounds on monkey ciliary muscle in vitro. Nonadrenergic, noncholinergic relaxation of bovine iris sphincter: role of endogenous nitric oxide. Chuman H Chuman T Nao-i N Different responsiveness to nitric oxide-cyclic guanosine monophosphate pathway in cholinergic and tachykinergic contractions of the rabbit iris sphincter muscle. Nitric oxide-sensitive and -insensitive contractions of the isolated rabbit iris sphincter muscle. Endogenous regulation of human Schlemm's canal cell volume by nitric oxide signaling.

Alterations of ocular nitric oxide synthase in human glaucoma. Decreased nitric oxide production in primary open-angle glaucoma. Eur J Ophthalmol. Nitric oxide proxies and ocular perfusion pressure in primary open angle glaucoma. Br J Ophthalmol. Amino acid pattern in human aqueous humor of patients with senile cataract and primary open-angle glaucoma.

Ophthalmic Res. Weiss J Frankl SA Flammer J No difference in genotype frequencies of polymorphisms of the nitric oxide pathway between Caucasian normal and high tension glaucoma patients. Mol Vis. Nathanson JA. Nitrovasodilators as a new class of ocular hypotensive agents. J Pharmacol Exp Ther. J Ocul Pharmacol Ther.