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Endothelin-1 role in human eye: a review.

Salvatore S, Vingolo EM - J Ophthalmol (2011)

Bottom Line: In addition to its direct vasoconstrictor effects, enhanced levels of ET-1 may contribute to endothelial dysfunction through inhibitory effects on nitric oxide (NO) production.Experimental studies have shown that chronic ET-1 administration to the optic nerve immediately behind the globe causes neuronal damage, activation of astrocytes, the major glial cell in the anterior optic nerve, and upregulation of endothelin B receptors.This paper outlines the ubiquitous role of endothelin and its potential involvement in ophthalmology.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, University "La Sapienza", Polo Pontino, Latina, Italy.

ABSTRACT
Endothelin is a potent vasoactive peptide occurring in three isotypes, ET-1, ET-2, and ET-3. Through its two main receptors, endothelin A and endothelin B, it is responsible for a variety of physiological functions, primarily blood flow control. Recent evidence from both human and animal models shows involvement of endothelin in diabetes, retinal circulation, and optic neuropathies. Increased circulating levels of endothelin-1 (ET-1) have been found in patients with diabetes, and a positive correlation between plasma ET-1 levels and microangiopathy in patients with type-2 diabetes has been demonstrated. In addition to its direct vasoconstrictor effects, enhanced levels of ET-1 may contribute to endothelial dysfunction through inhibitory effects on nitric oxide (NO) production. Experimental studies have shown that chronic ET-1 administration to the optic nerve immediately behind the globe causes neuronal damage, activation of astrocytes, the major glial cell in the anterior optic nerve, and upregulation of endothelin B receptors. This paper outlines the ubiquitous role of endothelin and its potential involvement in ophthalmology.

No MeSH data available.


Related in: MedlinePlus

Potential mechanism of endothelin (ET) and ET receptor-mediated actions causing retinal ganglion cell (RGC) loss. Optic nerve astrocytes may become activated via ET actions, leading to extracellular matrix (ECM) changes in the optic nerve head and eventual RGC loss. Figure adapted from Chauhan BC  [50].
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fig3: Potential mechanism of endothelin (ET) and ET receptor-mediated actions causing retinal ganglion cell (RGC) loss. Optic nerve astrocytes may become activated via ET actions, leading to extracellular matrix (ECM) changes in the optic nerve head and eventual RGC loss. Figure adapted from Chauhan BC [50].

Mentions: Open angle glaucoma is the most common optic neuropathy causing retinal ganglion cell (RGC) soma and axon loss, optic nerve head (ONH) structural loss, and visual field damage. Elevated intraocular pressure (IOP) is the most potent risk factor known for causing glaucomatous damage. Decades of experimental and clinical research consolidated the notion that lowering IOP has a favourable impact in the majority of patients with glaucoma. This has been confirmed in randomized clinical trials that included untreated control arms [53]. How IOP can lead to structural damage and produce clinical glaucoma is not fully understood. Much evidence points to the ONH, consisting of RGC axons, blood vessels, connective tissues and glia, as the primary site of damage in glaucoma [54]. It is likely that the microenvironment in the ONH reacts to stressors such as IOP and other potential IOP-dependent or IOP-independent factors, such as ischemia, to ultimately cause RGC axonal damage (Figure 3). The potential of endogenous vasoconstrictors to cause ischemic insult in the ONH was proposed many years ago and endothelin represents one vasoconstrictor agent with a possible role in glaucoma and other neurodegenerative diseases (Figure 3). An impairment of the anterior optic nerve microcirculation has been suspected to contribute and/or to be a causal factor in a variety of optic neuropathies. Thus, endothelins that produce dose-dependent vasoconstriction in various vascular beds, including the anterior optic nerve microvasculature, become likely candidates able to produce neural damage. Indeed, these peptides have been shown to produce localized vasoconstriction when injected directly into perivascular cerebral tissues in vivo and to result in regional ischemic damage of the brain nervous tissue [55].


Endothelin-1 role in human eye: a review.

Salvatore S, Vingolo EM - J Ophthalmol (2011)

Potential mechanism of endothelin (ET) and ET receptor-mediated actions causing retinal ganglion cell (RGC) loss. Optic nerve astrocytes may become activated via ET actions, leading to extracellular matrix (ECM) changes in the optic nerve head and eventual RGC loss. Figure adapted from Chauhan BC  [50].
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3065050&req=5

fig3: Potential mechanism of endothelin (ET) and ET receptor-mediated actions causing retinal ganglion cell (RGC) loss. Optic nerve astrocytes may become activated via ET actions, leading to extracellular matrix (ECM) changes in the optic nerve head and eventual RGC loss. Figure adapted from Chauhan BC [50].
Mentions: Open angle glaucoma is the most common optic neuropathy causing retinal ganglion cell (RGC) soma and axon loss, optic nerve head (ONH) structural loss, and visual field damage. Elevated intraocular pressure (IOP) is the most potent risk factor known for causing glaucomatous damage. Decades of experimental and clinical research consolidated the notion that lowering IOP has a favourable impact in the majority of patients with glaucoma. This has been confirmed in randomized clinical trials that included untreated control arms [53]. How IOP can lead to structural damage and produce clinical glaucoma is not fully understood. Much evidence points to the ONH, consisting of RGC axons, blood vessels, connective tissues and glia, as the primary site of damage in glaucoma [54]. It is likely that the microenvironment in the ONH reacts to stressors such as IOP and other potential IOP-dependent or IOP-independent factors, such as ischemia, to ultimately cause RGC axonal damage (Figure 3). The potential of endogenous vasoconstrictors to cause ischemic insult in the ONH was proposed many years ago and endothelin represents one vasoconstrictor agent with a possible role in glaucoma and other neurodegenerative diseases (Figure 3). An impairment of the anterior optic nerve microcirculation has been suspected to contribute and/or to be a causal factor in a variety of optic neuropathies. Thus, endothelins that produce dose-dependent vasoconstriction in various vascular beds, including the anterior optic nerve microvasculature, become likely candidates able to produce neural damage. Indeed, these peptides have been shown to produce localized vasoconstriction when injected directly into perivascular cerebral tissues in vivo and to result in regional ischemic damage of the brain nervous tissue [55].

Bottom Line: In addition to its direct vasoconstrictor effects, enhanced levels of ET-1 may contribute to endothelial dysfunction through inhibitory effects on nitric oxide (NO) production.Experimental studies have shown that chronic ET-1 administration to the optic nerve immediately behind the globe causes neuronal damage, activation of astrocytes, the major glial cell in the anterior optic nerve, and upregulation of endothelin B receptors.This paper outlines the ubiquitous role of endothelin and its potential involvement in ophthalmology.

View Article: PubMed Central - PubMed

Affiliation: Department of Ophthalmology, University "La Sapienza", Polo Pontino, Latina, Italy.

ABSTRACT
Endothelin is a potent vasoactive peptide occurring in three isotypes, ET-1, ET-2, and ET-3. Through its two main receptors, endothelin A and endothelin B, it is responsible for a variety of physiological functions, primarily blood flow control. Recent evidence from both human and animal models shows involvement of endothelin in diabetes, retinal circulation, and optic neuropathies. Increased circulating levels of endothelin-1 (ET-1) have been found in patients with diabetes, and a positive correlation between plasma ET-1 levels and microangiopathy in patients with type-2 diabetes has been demonstrated. In addition to its direct vasoconstrictor effects, enhanced levels of ET-1 may contribute to endothelial dysfunction through inhibitory effects on nitric oxide (NO) production. Experimental studies have shown that chronic ET-1 administration to the optic nerve immediately behind the globe causes neuronal damage, activation of astrocytes, the major glial cell in the anterior optic nerve, and upregulation of endothelin B receptors. This paper outlines the ubiquitous role of endothelin and its potential involvement in ophthalmology.

No MeSH data available.


Related in: MedlinePlus