Endothelin-1 and Nitric Oxide levels in exudative age-related macular degeneration

Abstract

Purpose:To evaluate plasma levels of endothelin-1 (ET-1) and nitric oxide (NO) in patients with exudative age-related macular degeneration (AMD).Methods:In this study, ET-1 levels, as well as nitrite plus nitrate concentrations as an indicator of plasma NO level, were measured in the plasma of 20 subjects with exudative AMD and compared with 20 healthy age and sex matched controls.Results:Mean plasma ET-1 level was significantly higher in exudative AMD patients as compared to control subjects (0.35 ± 0.06 fmol/ml versus 0.17 ± 0.03 fmol/ml, P = 0.015). Patients with exudative AMD also showed significantly lower mean plasma levels of nitrite plus nitrate as compared to the controls (58.9 ± 2.7 µmol/l versus 82.6 ± 5.9 µmol/l, P = 0.001).Conclusion:Increased concentrations of ET-1 and reduced levels of NO in the plasma may suggest an imbalance between vasoconstrictor and vasodilator agents, respectively, as a reflection of endothelial dysfunction in the pathogenesis of AMD. These findings may also imply the role of vasoconstriction in exudative AMD.

Biomarkers of Neurodegeneration and Precision Therapy in Retinal Disease

“…Authors highlighted that this specific increase would reflect a severe vascular disturbance ( Machalińska et al, 2011 ). With respect to oxidative stress, Totan and coworkers showed the presence of increased Endothelin-1 (ET-1) and reduced Nitric Oxide (NO) plasmatic levels in AMD, suggesting an imbalance between vasoconstrictor and vasodilator agents, possibly reflecting either an endothelial dysfunction in AMD pathogenesis or a role of vasoconstriction in exudative AMD ( Totan et al, 2015 ). Another study showed significant elevation of serum concentrations of IL-1α, IL-1β, IL-4, IL-5, IL-10, IL-13, and IL-17 in AMD patients compared to control subjects ( Nassar et al, 2015 ).…”

Choroidal Neovascularization: Mechanisms of Endothelial Dysfunction

“…Endothelial cells produce a physiological balance of vasoactive substances to regulate vascular function, such as the vasoconstrictor endothelin-1 (ET-1) and the vasodilator nitric oxide (NO). ET-1 levels increase while NO availability decreases during aging, resulting in increased vasoconstriction and impaired vasodilation, which could lead to constriction of smaller vessels associated with ischemia of the choriocapillaris (decreased choroidal blood flow) seen in severe dry AMD (Stauffer et al, 2008; El Assar De La Fuente et al, 2012; Totan et al, 2015). Decreased choroidal blood flow in dry AMD has been correlated with severity of dry AMD, and could increase the risk for ischemia and hypoxia leading to choroidal neovascularization in wet AMD (Grunwald et al, 2005).…”

“…Decreased choroidal blood flow in dry AMD has been correlated with severity of dry AMD, and could increase the risk for ischemia and hypoxia leading to choroidal neovascularization in wet AMD (Grunwald et al, 2005). Totan et al showed that patients with wet AMD exhibit increased ET-1 and decreased NO in the plasma, indicating that endothelial dysfunction is apparent in these patients (Totan et al, 2015). With age being the largest risk factor for AMD, it is not surprising that age-related vascular dysfunction would contribute to the progression of AMD, as seen also in a number of age-related diseases (Ehrlich et al, 2009; Akpek and Smith, 2013).…”

Nitrosative Stress in Retinal Pathologies: Review

“…Although the exact mechanism of AMD is still unknown, it has been established that advanced age is the main risk factor but that other factors could also be involved. These factors include cigarette smoking, elevated cholesterol levels, systemic arterial hypertension and stiffness, ultraviolet exposure, cardiovascular disease, race, gender and family history [77].…”

“…A vascular theory, that includes abnormalities of the choroidal circulation has been suggested to contribute to AMD development [78]. Even though, the precise role of NO in the onset of AMD has not been clearly determined, the involvement of oxidative stress and NO as a part of the vascular theory has been reported [77]. Both factors (oxidative stress and NO alterations) can contribute to the vascularization decrease of choriocapillaris and apoptosis, to the increasing formation of drusen and to the increased VEGF release from the retinal pigment epithelium cells [79].…”