Endothelin-1 Synthesis and Secretion in Human Retinal Pigment Epithelial Cells (ARPE-19): Differential Regulation by Cholinergics and TNF-α

Narayan, Santosh; Prasanna, Ganesh; Krishnamoorthy, Raghu R; Zhang, Xinyu; Yorio, Thomas

doi:10.1167/iovs.03-0387

Cited by 48 publications

(25 citation statements)

References 46 publications

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“…TNF-α was induced in human RPE cells by oxidative stress [49]. This cytokine was further described to stimulate the increase in IL-6, IL-8, and MCP-1 [50,51,52], and the expression of ICAM-1 and VCAM-1 [53]. Moreover, TNF-α causes cytosolic to nuclear translocation of NF-κB and increases its DNA-binding activity in human RPE cells [54], which in turn accounts for the transcription of pro-inflammatory genes [55].…”

Section: Discussionmentioning

confidence: 99%

Complement Stimulates Retinal Pigment Epithelial Cells to Undergo Pro-Inflammatory Changes

Lueck

Busch²,

Moss³

et al. 2015

Ophthalmic Res

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Background/Aims: We examined the effect of human complement sera (HCS) on retinal pigment epithelial (RPE) cells with respect to pro-inflammatory mediators relevant in early age-related macular degeneration (AMD). Methods: RPE cells were treated with complement-containing HCS or with heat-inactivated (HI) HCS or C7-deficient HCS as controls. Cells were analysed for C5b-9 using immunocytochemistry and flow cytometry. Interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 (MCP-1) were quantified by ELISA and RT-PCR. Tumour necrosis factor-a (TNF-a), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), were analysed by Western blotting. The intracellular distribution of nuclear factor (NF)-κB was investigated by immunofluorescence. Results: A concentration-dependent increased staining for C5b-9 but no influence on cell viability was observed after HCS treatment. ELISA and RT-PCR analysis revealed elevated secretion and expression of IL-6, IL-8, and MCP-1. Western blot analysis showed a concentration-dependent increase in ICAM-1, VCAM-1, and TNF-a in response to HCS, and immunofluorescence staining revealed nuclear translocation of NF-κB. Conclusion: This study suggests that complement stimulates NF-κB activation in RPE cells that might further create a pro-inflammatory environment. All these factors together may support early AMD development.

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Section: Discussionmentioning

confidence: 99%

Complement Stimulates Retinal Pigment Epithelial Cells to Undergo Pro-Inflammatory Changes

Lueck

Busch²,

Moss³

et al. 2015

Ophthalmic Res

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“…The release of ET-1 also increases during blood-retinal barrier breakdown (eg, after tumour necrosis factor-a treatment). 37 We previously localised ET-1 with an immunohistochemical analysis of epiretinal proliferative tissue from PVR membranes and reported the secretion of ET-1 by glial and RPE cells. Furthermore, these membranes may express ETA and ETB receptors.…”

Section: Discussionmentioning

confidence: 99%

Modelling postoperative visual acuity with and without proliferative vitreoretinopathy associated with primary rhegmatogenous retinal detachment

Roldán-Pallarés

Bravo-Llatas

Musa

et al. 2012

Eye

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Purpose To find models that will explain the variability in postoperative visual acuity (VA) (logarithmic: logMAR) associated with unilateral primary rhegmatogenous retinal detachment (RD). Methods This was a prospective clinical cohort study of 33 patients with proliferative vitreoretinopathy (PVR: PVRoC3) and 33 without PVR, all of whom were candidates for scleral buckling (SB) surgery. Central retinal artery (CRA) Doppler sonography parameters (peak systolic, end diastolic velocities and resistibility index) and intraocular pressure (IOP) were measured before SB. Immunoreactive endothelin-1 (IR-ET-1) levels in both plasma and subretinal fluid (SRF) were measured using a radioimmunoassay. Visual outcomes were analysed by stepwise multivariate linear regression. The preoperative parameters used in the analysis included RD duration, IOP, logMAR VA, CRA parameters, preoperative plasma levels and intraoperative levels of IR-ET-1 in the SRF. ConclusionsThe duration of RD and the levels of IR-ET-1 in the SRF appear to be the best explanatory variables in the models for 8-month-postoperative logMAR VA variability in RD patients. RD surgery should be performed as soon as possible to best preserve VA.

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“…Intraocular ET-1 concentrations may be higher if ET-1 is produced locally or diffuses into the eye from the retinal or choroidal vascular beds and/or from RPE cells. ET-1 synthesis and its secretion have been identified in human RPE cells [34], and there is evidence that RPE is a source of ET-1 in the retina and that its release increases during blood-retinal barrier breakdown, (after tumor necrosis factor-α treatment) [34], as in PVR, The RPE playing a role in endothelin-mediated photoreceptor survival cannot be excluded, because this retinal layer contains ET-1, preproET-1, and ETA immunoreactivities [35]. RPE and glial cells are the main contributors to membrane formation and contraction in PVR.…”

Section: Discussionmentioning

confidence: 99%

Preoperative duration of retinal detachment and subretinal immunoreactive endothelin-1: repercussion on logarithmic visual acuity

Roldán-Pallarés

Musa

Bravo-Llatas

et al. 2009

Graefes Arch Clin Exp Ophthalmol

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Preoperative RD duration showed statistically significant positive correlations with pre- and with postoperative 8 months LogMAR VAs in both the no-PVR and the PVR groups and with IR-ET-1 measurements (plasma and SRF: lower correlations) only in the no-PVR group. These findings support the idea of doing primary and prompt vitrectomy for RD and perhaps using coadjutant pharmacologic therapy in order to improve visual results.

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Endothelin-1 Synthesis and Secretion in Human Retinal Pigment Epithelial Cells (ARPE-19): Differential Regulation by Cholinergics and TNF-α

Cited by 48 publications

References 46 publications

Complement Stimulates Retinal Pigment Epithelial Cells to Undergo Pro-Inflammatory Changes

Complement Stimulates Retinal Pigment Epithelial Cells to Undergo Pro-Inflammatory Changes

Modelling postoperative visual acuity with and without proliferative vitreoretinopathy associated with primary rhegmatogenous retinal detachment

Preoperative duration of retinal detachment and subretinal immunoreactive endothelin-1: repercussion on logarithmic visual acuity

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