research

 A Novel Nitric Oxide Releasing Prostaglandin Analog, NCX 125, Reduces Intraocular Pressure in Rabbit, Dog, and Primate Models of Glaucoma

Abstract

Purpose: Nitric oxide (NO) is involved in a variety of physiological processes including ocular aqueous humor dynamics by targeting mechanisms that are complementary to those of prostaglandins. Here, we have characterized a newly synthesized compound, NCX 125, comprising latanoprost acid and NO-donating moieties.

Methods: NCX 125 was synthesized and tested in vitro for its ability to release functionally active NO and then compared with core latanoprost for its intraocular pressure (IOP)-lowering effects in rabbit, dog, and nonhuman primate models of glaucoma.

Results: NCX 125 elicited cGMP formation (EC50 = 3.8 ± 1.0 μM) in PC12 cells and exerted NO-dependent iNOS inhibition (IC50 = 55 ± 11 μM) in RAW 264.7 macrophages. NCX 125 lowered IOP to a greater extent compared with equimolar latanoprost in: (a) rabbit model of transient ocular hypertension (0.030% latanoprost, not effective; 0.039% NCX 125, ∆max = −10.6 ± 2.3 mm Hg), (b) ocular hypertensive glaucomatous dogs (0.030% latanoprost, ∆max= −6.7 ± 1.2 mm Hg; 0.039% NCX 125, ∆max = −9.1 ± 3.1 mm Hg), and (c) laser-induced ocular hypertensive non-human primates (0.10% latanoprost, ∆max = −11.9 ± 3.7 mm Hg, 0.13% NCX 125, ∆max = −16.7 ± 2.2 mm Hg). In pharmacokinetic studies, NCX 125 and latanoprost resulted in similar latanoprost-free acid exposure in anterior segment ocular tissues.

Conclusions: NCX 125, a compound targeting 2 different mechanisms, is endowed with potent ocular hypotensive effects. This may lead to potential new perspectives in the treatment of patients at risk of glaucoma.

This year the World Glaucoma Congress (WGC) is taking place in the United States (Boston, MA) from July 8th to 11th. Dr. Ritch will be there, as will Marcel and I.

I believe all of you know, or know of, Dr. Ritch. Marcel is a key founder of the International Society for Self-Tonometry (ISST), of which Dr. Ritch is Honorary Chairman. Marcel is a driving force behind getting me and several other self-tonometrists together in Boston.

Are there limits to the duration of high quality of life? Are there limits to healthy life for a human brain? [These questions are relevalant for vision as well as cognitive health because the optic nerve is part of the central nervous system.]

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. Although the etiology and pathogenesis of AMD remain largely unclear, a complex interaction of genetic and environmental factors is thought to exist. AMD pathology is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium, and Bruch’s membrane, as well as, in some cases, alterations in choroidal capillaries. Recent research on the genetic and molecular underpinnings of AMD brings to light several basic molecular pathways and pathophysiological processes that might mediate AMD risk, progression, and/or response to therapy.

The Ayurvedic herb saffron may hold one of the keys to preventing the loss of sight in old age – and may even help to improve vision in people suffering certain blinding eye diseases.

Research by Professor Silvia Bisti of the ARC Centre of Excellence in Vision Science (The Vision Centre) and University of L’Aquila, Italy, has established that saffron has remarkable effects on the genes which regulate the performance of the eye’s key vision cells.

I want to highlight three different approaches to performing home eye pressure monitoring (self-tonometry). Normally, I focus most of my attention in my blog on the approach I use. However, I thought it would be educational to contrast my approach with two other approaches. I'll discuss each one, but to get us started I would like to give each method a name as shown below:

 I received this comment in an email today: 

"It is very good that I started participating in this intraocular pressure monitoring project, because otherwise I would not know what is going on with my eye pressure. Now, it is even more evident for me that my eyes should undergo additional checks."