Elevated Plasma Endothelin-1 Levels in Normal Tension Glaucoma and Primary Open-Angle Glaucoma: A Meta-Analysis

Li, Shengjie; Zhang, Aiping; Cao, Wenjun; Sun, Xinghuai

doi:10.1155/2016/2678017

Cited by 43 publications

(30 citation statements)

References 30 publications

(43 reference statements)

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“…In 2016, Li et al [24] performed a meta-analysis in order to combine and summarize the results from several studies analyzing ET-1 plasma levels in NTG patients (7 studies, 212 NTG, 164 controls) and POAG (5 studies, 160 POAG, 174 controls), and also to clarify the association between ET-1 plasma levels and the risk for the mentioned types of glaucoma. They found statistically significant higher ET-1 plasma concentrations in glaucoma patients than in the control group, with a 0.63 pg/ mL mean difference (p = 0.02) in the POAG group, and 0.60 pg/mL (p = 0.007) in the NTG patients.…”

Section: Resultsmentioning

confidence: 99%

“…ET-1 plasma concentrations in POAG patients reported in other studies. were associated with significantly higher risk for NTG and POAG [24]. In 2016, Kosior-Jarecka et al [27] reported positive correlation between ET-1 plasma levels and visual field defects.…”

Section: Resultsmentioning

confidence: 99%

“…Intraocular ET-1 injections induce chronic ischemia of the optic nerve that causes retinal ganglion cell-specific death and glaucomatous cupping of the optic nerve head (ONH). A recent meta-analysis [24] shows that statistically significantly high ET-1 plasma levels in glaucoma patients are associated with significantly higher risk for NTG and POAG.…”

Section: Introductionmentioning

confidence: 99%

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Plasma endothelin-1 and endothelin-A receptor concentrations in patients with primary open-angle glaucoma

Mihaylova

Petkova

Rankova-Yotova

et al. 2017

Biotechnology & Biotechnological Equipment

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Endothelin-1 (ET-1) is a potent vasoconstrictor and is considered to have a key role in the regulation of ocular perfusion and glaucoma pathogenesis. High ET-1 and ET A -receptor levels are reported in patients with primary open-angle glaucoma (POAG). We compared the mean plasma ET-1 and ET Areceptor concentration of controls and patients with early and advanced POAG stage, and assessed the correlation with the retinal nerve fibre layer (RNFL) thickness. The study included a total of 75 participants, aged 45-83 years: 25 (controls), 22 (early glaucoma) and 28 (advanced glaucoma). The plasma concentration of ET-1 and ET A -receptor was determined by enzyme-linked immunosorbent assay. The RNFL thickness was evaluated with spectral-domain optical coherence tomography. The mean ET-1 concentration was lower in the control group (4.88 § 1.75 pg/mL) than in the early and advanced POAG group (6.33 § 2.38 and 6.34 § 1.56 pg/mL). Statistically significant difference was found between the mean ET-1 concentrations in controls and glaucoma patients (p = 0.029 -early glaucoma, p = 0.018 -advanced glaucoma), and no significant difference was observed between the two POAG groups (p = 0.998). The mean ET A -receptor concentration was highest in the control group (1209.28 § 314.48 pg/mL) and the differences between the three groups were significant. Significant relationship was found only between ET-1 and RNFL. This study demonstrated the role of ET-1 in glaucoma pathogenesis based on the observed significant high ET-1 and ET A -receptor plasma levels in POAG patients. A new therapeutical approach needs to be considered in some patients.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Plasma endothelin-1 and endothelin-A receptor concentrations in patients with primary open-angle glaucoma

Mihaylova

Petkova

Rankova-Yotova

et al. 2017

Biotechnology & Biotechnological Equipment

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“…Single nucleotide polymorphisms (SNPs) in both the ET-1 and ET A receptor genes that affected ET-1 plasma concentrations and higher ET-1 levels correlated with increased visual field damage 42 . A recent meta-analysis that included seven studies (212 cases, 164 controls) for normal tension glaucoma and six studies (160 cases, 174 controls) for the POAG analysis demonstrated increased circulating ET-1 levels in glaucoma patients, compared to control subjects 43 .…”

Section: Discussionmentioning

confidence: 99%

Endothelin-1 Mediated Decrease in Mitochondrial Gene Expression and Bioenergetics Contribute to Neurodegeneration of Retinal Ganglion Cells

Chaphalkar

Stankowska

et al. 2020

Sci Rep

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Endothelin-1 (ET-1) is a vasoactive peptide that is elevated in aqueous humor as well as circulation of primary open angle glaucoma (POAG) patients. ET-1 has been shown to promote degeneration of optic nerve axons and apoptosis of retinal ganglion cells (RGCs), however, the precise mechanisms are still largely unknown. In this study, RNA-seq analysis was used to assess changes in ET-1 mediated gene expression in primary RGCs, which revealed that 23 out of 156 differentially expressed genes (DEGs) had known or predicted mitochondrial function, of which oxidative phosphorylation emerged as the topmost enriched pathway. ET-1 treatment significantly decreased protein expression of key mitochondrial genes including cytochrome C oxidase copper chaperone (COX17) and ATP Synthase, H + transporting, Mitochondrial Fo Complex (ATP5H) in primary RGCs and in vivo following intravitreal ET-1 injection in rats. A Seahorse ATP rate assay revealed a significant decrease in the rate of mitochondrial ATP production following ET-1 treatment. IOP elevation in Brown Norway rats showed a trend towards decreased expression of ATP5H. Our results demonstrate that ET-1 produced a decrease in expression of vital components of mitochondrial electron transport chain, which compromise bioenergetics and suggest a mechanism by which ET-1 promotes neurodegeneration of RGCs in glaucoma. Glaucoma is an optic neuropathy with an approximate prevalence of 60.5 million people worldwide and is projected to reach 111 million by 2040 1,2 .The disease is commonly associated with elevated intraocular pressure (IOP), accompanied by optic nerve degeneration and loss of retinal ganglion cells (RGCs) 3,4. RGC death via apoptosis is a culminating event in the pathophysiology of glaucoma, stemming from optic nerve axonal injury, leading to visual field loss. Elevated IOP is a major risk factor in primary open-angle-glaucoma and current therapeutic approaches are aimed at lowering IOP with medications, laser treatment, or surgery 5,6. However in some patients, the progression of the disease continues to occur slowly 7 despite lowering IOP, hence there is a compelling need for neuroprotection of RGCs and optic nerve axons and as an additional therapeutic modality. The molecular changes occurring specifically in the RGCs, during the progression of glaucoma, contributing to neurodegeneration, are still poorly understood; hence identifying new therapeutic targets could provide more efficacious neuroprotective treatments. ET-1 is a 21 amino acid vasoactive peptide that acts through two G-protein coupled receptors namely, ET A and ET B receptors, to produce diverse effects in various ocular tissues 8-11. A growing body of evidence suggests that endothelins and their receptors are major contributors to neuronal damage in glaucoma 11-16. The role of endothelins in glaucomatous neurodegeneration has been the subject of several review articles 12,17,18. However, the detailed cellular and molecular mechanisms that contribute to ET-1 mediated-neurodegeneration are not

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“…One important factor is a disturbed ocular blood flow. Some papers indicated that elevated plasma endothelin-1, which is known as a vasoconstrictor that increases under hypoxia, is involved in patients with NTG [28] , and a local increase of endothelin-1 can result in the occurrence of retinal vein occlusion through increased retinal venous pressure [29] . The pathomechanisms of NTG and POAG are different, and this needs further investigation; however, atherosclerosis or systemic hypertension, besides the disturbed autoregulation of optic nerve head circulation in patients with NTG and POAG, might induce CRVO.…”

Section: Discussionmentioning

confidence: 99%

Clinical Features of Japanese Patients with Central Retinal Vein Occlusion Complicated by Normal-Tension Glaucoma: A Retrospective Study

Fukumoto¹,

Sato²,

Oku³

et al. 2017

Ophthalmologica

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Purpose: The association of central retinal vein occlusion (CRVO) with primary open-angle glaucoma (POAG) or ocular hypertension has been reported, and lowering intraocular pressure (IOP) helps to improve the retinal circulation in eyes with CRVO. However, the clinical features of CRVOs with normal-tension glaucoma (NTG) are not well known. Therefore, we investigated Japanese CRVO patients with NTG. Methods: We retrospectively investigated 234 CRVO patients over 5 years, with follow-ups of more than 12 months, and evaluated the prevalence of glaucoma. Results: Of the 234 CRVO patients, 18 (7.7%) were diagnosed with NTGs (n = 10) or POAGs (n = 8). Seven POAG (87.5%) and 3 NTG (30%) patients had systemic hypertension. At the initial CRVO evaluation, 6 NTGs showed a significantly increased IOP; mean IOP was 13.3 mm Hg before CRVO, 16.2 mm Hg at CRVO, and 13.5 mm Hg at the final visit. Conclusions: The proportion of NTGs with systemic hypertension was low. IOP of NTG patients was significantly elevated at the initial CRVO evaluation, even in the presence of anti-glaucoma drugs.

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Elevated Plasma Endothelin-1 Levels in Normal Tension Glaucoma and Primary Open-Angle Glaucoma: A Meta-Analysis

Cited by 43 publications

References 30 publications

Plasma endothelin-1 and endothelin-A receptor concentrations in patients with primary open-angle glaucoma

Plasma endothelin-1 and endothelin-A receptor concentrations in patients with primary open-angle glaucoma

Endothelin-1 Mediated Decrease in Mitochondrial Gene Expression and Bioenergetics Contribute to Neurodegeneration of Retinal Ganglion Cells

Clinical Features of Japanese Patients with Central Retinal Vein Occlusion Complicated by Normal-Tension Glaucoma: A Retrospective Study

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