Partial Antagonism of Endothelin 1–Induced Vasoconstriction in the Human Choroid by Topical Unoprostone Isopropyl

Polska, Elżbieta; Doelemeyer, Arno; Luksch, Alexandra; Ehrlich, Paulina; Kaehler, Nils; Percicot, Christine L.; Lambrou, George N.; Schmetterer, Leopold

doi:10.1001/archopht.120.3.348

Cited by 31 publications

(22 citation statements)

References 29 publications

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Section: Improvement Of Ocular Blood Flow By Prostaglandin F Analoguesmentioning

confidence: 96%

“…In this placebo-controlled study, it was shown that intravenous injection of ET-1 decreased choroidal blood flow. This effect was significantly blunted when topical unoprostone was coadministered (Polska et al, 2002).Different animal studies revealed a direct, IOPindependent effect of PG analogues on blood flow. In rabbits ET-1 decreased optic nerve head blood flow.…”

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confidence: 96%

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Endothelin antagonism as an active principle for glaucoma therapy

Rosenthal

Fromm

2011

British J Pharmacology

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Endothelin, the most potent vasoactive peptide known to date, has been suggested to play a potential role in the pathogenesis of open-angle glaucoma. Open-angle glaucoma is the most common optic nerve head neuropathy and is associated with a loss of retinal ganglion cells and visual field damage. Although an increased intraocular pressure is a major risk factor for glaucomatous optic neuropathy, other factors such as a reduced ocular blood flow play an important role for appearance of the disease. Thus, treatment of glaucoma is focused on lowering of intraocular pressure and preventing the occurrence or progression of glaucomatous optic neuropathy. Endothelin participates in the regulation of intraocular pressure by an effect on trabecular outflow, the main route for aqueous humour outflow from the eye. Trabecular outflow is modulated by trabecular meshwork contractility which is affected by endothelin. In addition to the effects of endothelin in the anterior part of the eye, the vasoconstrictor causes a decrease in ocular blood flow followed by pathological changes in the retina and the optic nerve head which is assumed to contribute to the degeneration of retinal ganglion cells. In sum, inhibition of endothelin signalling leads to lowering of intraocular pressure and exerts neuroprotective effects. Thus, endothelin antagonism in the eye represents a promising approach for pharmacological treatment of glaucoma. AbbreviationsECE, endothelin-converting enzyme; ET-1, endothelin-1; ETA receptor, endothelin receptor A; ETB receptor, endothelin receptor B; FP receptor, prostaglandin F receptor; IOP, intraocular pressure; MLCK, myosin light chain kinase; MMP, matrix-metalloproteinase; OBF, ocular blood flow; PG, prostaglandin; ROCK, Rho kinase; RGC, retinal ganglion cell IntroductionEndothelin-1 (ET-1), the most potent vasoconstrictor known to date, is expressed in many organs and tissues and has been shown to play an important role in vascular homeostasis (Yanagisawa et al., 1988) as well as in a variety of pathological processes (Levin, 1995).In the human eye endothelin is detectable in the posterior part, especially in the choroid, retinal blood vessels, retinal pigment epithelium and optic nerve (Wollensak et al., 1998;Narayan et al., 2004). The precise source of endothelin in the posterior segment of the eye remains unclear. One possible source is the retinal pigment epithelium, which secretes ET-1 towards the basolateral side, suggesting an involvement in the regulation of choroidal blood flow (Narayan et al., , 2004Dibas et al., 2005a). The ET-1 synthesis and release from optic nerve head astrocytes as seen in cultured human cells may contribute to the signal in the optic nerve (Desai et al., 2004).In the anterior part of the eye, ET-1 was found in the iris, non-pigmented ciliary epithelium, ciliary muscle, as well as in the trabecular meshwork, endothelial cells lining Schlemm's canal and corneal epithelium (Wollensak et al., 1998;Fernandez-Durango et al., 2003). Apart from its localization in ocular tissues, ...

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Section: Improvement Of Ocular Blood Flow By Prostaglandin F Analoguesmentioning

confidence: 96%

mentioning

confidence: 96%

Endothelin antagonism as an active principle for glaucoma therapy

Rosenthal

Fromm

2011

British J Pharmacology

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“…Further, a possible antagonistic effect between endothelin 1 and unoprostone in the choroidal vasculature has been reported [86]. Travoprost.…”

Section: Prostaglandismentioning

confidence: 96%

Evolving Paradigms in the Medical Treatment of Glaucoma

2004

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In the last 5 years, numerous novel ocular hypotensive agents have been introduced for the control of intraocular pressure (IOP). Clinicians now have more options than ever in medical therapy for the treatment of glaucoma and ocular hypertension. When selecting an ocular hypotensive medication for their patients, clinicians should consider not only the IOP-lowering efficacy of an agent but also the ability of the drug to achieve target levels of IOP that are low enough to stop the progression of glaucomatous damage. Other considerations should include how well the drug controls diurnal IOP, the likelihood of serious adverse events, the versatility of the medication for use as an adjunctive agent, as well as other potential attributes (e.g., neuroprotection).

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“…Compared to latanoprost, unoprostone seems to be less effective in extent and duration of IOP reduction [69]. Recent evidence suggests that topical applied unoprostone increases optic nerve head, choroidal and retinal blood flow and an antagonistic effect of endothelin-1 induced vasoconstriction in the human choroid has been observed [70,71]. No darkening of the iris colour is induced.…”

Section: Prostaglandinsmentioning

confidence: 99%

Topical Drug Therapy in Glaucoma

Resch

Garhöfer

2006

Wien Med Wochenschr

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Glaucoma is defined as a progressive optic neuropathy involving characteristic structural changes in the optic nerve head and corresponding visual field defects. Elevated intraocular pressure (IOP) is a major risk and causative factor for glaucomatous optic neuropathy. Although mechanisms other than elevated IOP may contribute to the underlying pathophysiology of glaucoma, reducing IOP remains the primary goal of therapy. Recent clinical studies have shown that decreasing the IOP can delay, or in some cases prevent progression of this chronic ocular disease. Over the past decade, several new medical therapies have become available for the treatment of glaucoma. In this article a review of topical glaucoma therapy is presented.

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Partial Antagonism of Endothelin 1–Induced Vasoconstriction in the Human Choroid by Topical Unoprostone Isopropyl

Cited by 31 publications

References 29 publications

Endothelin antagonism as an active principle for glaucoma therapy

Endothelin antagonism as an active principle for glaucoma therapy

Evolving Paradigms in the Medical Treatment of Glaucoma

Topical Drug Therapy in Glaucoma

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