Immunoreactive Endothelin-1 in the Vitreous Humor and Epiretinal Membranes of Patients With Proliferative Diabetic Retinopathy

Roldán-Pallarés, Manuela; Rollín, R.; Martínez-Montero, Juan Carlos; Fernández-Cruz, A; Bravo-Llata, Carmen; Fernández‐Durango, Raquel

doi:10.1097/01.iae.0000231376.76601.40

Cited by 36 publications

(54 citation statements)

References 46 publications

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“…18 Moreover, ET-1 increases in the vitreous humor and epiretinal membranes of PVR patients. 19 Therefore, astrocytes and ET-1 could play a central role in the pathogenesis of PVR.…”

mentioning

confidence: 99%

Blockade of Endothelinergic Receptors Prevents Development of Proliferative Vitreoretinopathy in Mice

Iribarne

Ogawa

Torbidoni

et al. 2008

The American Journal of Pathology

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Proliferative vitreoretinopathy (PVR) is characterized by severe glial remodeling. Glial activation and proliferation that occur in brain diseases are modulated by endothelin-1 (ET-1) and its receptor B (ETR-B). Because retinal astrocytes contain ET-1 and express ETR-B, we studied the changes of these molecules in an experimental mouse model of PVR and in human PVR. Both ET-1 and ETR-B immunoreactivities increased in mouse retina after induction of PVR with dispase. Epi-and subretinal outgrowths also displayed these immunoreactivities in both human and experimental PVR. Additionally, myofibroblasts and other membranous cell types showed both ET-1 and ETR-B immunoreactivities. In early stages of experimentally induced PVR, prepro-ET-1 and ETR-B mRNA levels increased in the retina. These mRNA levels also increased after retinal detachment (RD) produced by subretinal injection. Treatment of mice with tezosentan, an antagonist of endothelinergic receptors, reduced the histopathological hallmarks of dispase-induced PVR: retinal folding, epiretinal outgrowth, and gliosis. Our findings in human and in dispase-induced PVR support the involvement of endothelinergic pathways in retinal glial activation and the phenotypic transformations that underlie the growth of membranes in this pathology. Elucidating these pathways further will help to develop pharmacological treatments to prevent PVR. In addition, the presence of ET-1 and ETR-B in human fibrous membranes suggests that similar treatments could be helpful after PVR has been established.

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“…18 Moreover, ET-1 increases in the vitreous humor and epiretinal membranes of PVR patients. 19 Therefore, astrocytes and ET-1 could play a central role in the pathogenesis of PVR.…”

mentioning

confidence: 99%

Blockade of Endothelinergic Receptors Prevents Development of Proliferative Vitreoretinopathy in Mice

Iribarne

Ogawa

Torbidoni

et al. 2008

The American Journal of Pathology

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“…Moreover, ET-1 is secreted by glial and RPE cells, and ETA and ETB receptors are expressed in epiretinal proliferative tissue. 17 In our study, IR-ET-1 levels in the subretinal fluid (SRF) were more strongly associated with PVR (as a complication of RD) than with the preoperative duration of RD. 18 The purpose of this paper was to quantify the influence of several factors in predicting VA (expressed as logMAR) 8 months after surgery in patients who had primary rhegmatogenous RD with or without PVR.…”

Section: Introductionmentioning

confidence: 73%

“…Furthermore, these membranes may express ETA and ETB receptors. 17 The vascular upregulation of ETA receptors has been reported in experimental RD, 14 and the stimulation of these ETA receptors may contribute to the induction of cell proliferation. 38 In patients with RD and PVR, increased ET-1 may be a consequence of tissue hypoxia.…”

Section: Discussionmentioning

confidence: 99%

“…Both SRF and blood samples were collected in chilled tubes containing protease inhibitors. 6,17,18 Blood samples were centrifuged at 3000 r.p.m. for 20 min at 4 1C to obtain plasma.…”

Section: Observation Procedures and Outcome Measuresmentioning

confidence: 99%

“…IR-ET-1 measurements were taken from plasma and SRF samples as previously reported. 6,17,18,24 Briefly, IR-ET-1 was assayed in the laboratory by RIA, using polyclonal antibodies against synthetic ET-1 (Peninsula Laboratories, Merseyside, UK) at a 1 : 90 000 final dilution. The sensitivity of the RIA was 1 pg/ml.…”

Section: Observation Procedures and Outcome Measuresmentioning

confidence: 99%

See 2 more Smart Citations

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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Alterations in circulating angiogenic and anti‐angiogenic factors in type 2 diabetic patients with neuropathy

Motawi

Rizk

Ibrahim

et al. 2013

Cell Biochemistry & Function

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Diabetic peripheral neuropathy (DPN) is one of the most common diabetic chronic complications. There is an increased attention directed towards the role of angiogenic factors including vascular endothelial growth factor (VEGF) and anti-angiogenic factors including soluble endoglin (sEng) as contributors to diabetic microvascular complications including neuropathy. The purposes of this study were to determine the role of these angiogenesis regulators in the prognosis of DPN. The study group included 60 patients with type 2 diabetes mellitus (T2DM) and 20 clinically healthy individuals. The patients were divided into two groups. Group I included 20 T2DM patients without peripheral neuropathy, and Group II consisted of 40 T2DM patients with DPN. In all groups, plasma VEGF, sEng and endothelin-1 (ET-1), nitric oxide and ET-1 mRNA were estimated. Plasma levels of VEGF, sEng, ET-1 and nitric oxide were significantly elevated in diabetic patients (Groups I and II) compared with healthy control subjects, with a higher increase in their levels in patients with DPN compared with diabetic patients without peripheral neuropathy. Measurement of plasma levels of angiogenesis-related biomarkers in high-risk diabetic patients might identify who later develop DPN, thus providing opportunities for early detection and targets for novel treatments.

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Immunoreactive Endothelin-1 in the Vitreous Humor and Epiretinal Membranes of Patients With Proliferative Diabetic Retinopathy

Abstract: Diabetic patients with PDR and ERMs had the highest plasma and vitreous IR-ET-1 levels. ET-1 and its ETA and ETB receptors were present in ERMs. These data suggest that ET-1 is involved in diabetic vitreoretinal disease.

Cited by 36 publications

References 46 publications

Blockade of Endothelinergic Receptors Prevents Development of Proliferative Vitreoretinopathy in Mice

Blockade of Endothelinergic Receptors Prevents Development of Proliferative Vitreoretinopathy in Mice

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

Alterations in circulating angiogenic and anti‐angiogenic factors in type 2 diabetic patients with neuropathy

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