Immunohistochemical Evaluation of Idiopathic Epiretinal Membranes and In Vitro Studies on the Effect of TGF-β on Müller Cells

Bu, Shaochong; Kuijer, Roel; Worp, Roelofje J. van der; Postma, Gina; Lavalette, Victor W. Renardel de; Li, Xiaorong; Hooymans, Johanna M. M.; Los, Leonoor I.

doi:10.1167/iovs.14-15971

Cited by 56 publications

(67 citation statements)

References 43 publications

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“…According to previous reports, Müller glial cells and myofibroblasts constituting iERM tissues were positive for glial fibrillary acid protein (GFAP) and α-smooth muscle actin (α-SMA), respectively81516. Double labeling experiments revealed co-localization of (P)RR signal with GFAP, a glial cell marker (Fig.…”

Section: Resultssupporting

confidence: 58%

“…Histological analyses of iERM tissues indicated a variety of cells including glial cells, hyalocytes, fibroblasts and myofibroblasts181920. Among them, Müller glial cells, a main constituent cell type in iERM, are the most important cellular components required for membrane growth by intracellular signal transduction1519. Several studies described the involvement of cytokines and trophic factors in the pathogenesis of iERM4816212223.…”

Section: Resultsmentioning

confidence: 99%

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Pathologic Roles of Receptor-Associated Prorenin System in Idiopathic Epiretinal Membrane

Dong

Kanda

Noda

et al. 2017

Sci Rep

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Receptor-associated prorenin system (RAPS) refers to the pathogenic mechanism whereby prorenin binding to (pro)renin receptor [(P)RR] dually activates tissue renin-angiotensin system (RAS) and RAS-independent signaling via (P)RR. The aim of this study is to determine the association of RAPS with idiopathic epiretinal membrane (iERM). Reverse transcription-PCR indicated the expression of RAPS components, including (P)RR and Ang II type 1 receptor (AT1R), in iERM tissues and human Müller glial cell line. Double-labeling analyses demonstrated that (P)RR and AT1R were detected in cells positive for glial fibrillary acidic protein, a marker for glial cells, and co-localized with prorenin and angiotensinogen, respectively. Administration of prorenin to Müller glial cells enhanced mRNA expression of fibroblast growth factor 2, while Ang II application stimulated the expression of glial cell line-derived neurotrophic factor, nerve growth factor, and transforming growth factor-β1. These expression levels induced by prorenin or Ang II were reversed by (P)RR or AT1R blockade, respectively. Immunofluorescence revealed tissue co-localization of (P)RR and AT1R with the products of the upregulated genes in vitro. The present findings suggest the involvement of RAPS in the pathogenesis of iERM.

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Section: Resultssupporting

confidence: 58%

Section: Resultsmentioning

confidence: 99%

Pathologic Roles of Receptor-Associated Prorenin System in Idiopathic Epiretinal Membrane

Dong

Kanda

Noda

et al. 2017

Sci Rep

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“…Transforming growth factor-b induces the differentiation of these cells into a fibroblast-like phenotype and promotes their migration. 7,8 Characteristic cytokine profiles for the differentiation of fibroblasts and retinal glia are unknown, but we assume activated fibroblasts as a source, but not so evidently Müller glia cells, in the chronic phase of ERM formation. The cytokine profiles in our study are commensurate with an activation of fibrotic and inflammatory processes, which are associated with elevated levels of IL-6, IL-4, IL-1b, TNF-a, IL-10, IL-2, and INF-c (among others).…”

Section: Discussionmentioning

confidence: 99%

“…1,2,5 Müller glial cells are known to activate fibroblasts and to promote fibrotic changes within the eye, such as proliferative vitreoretinopathy (PVR) 3,6 and the formation of epiretinal membranes (ERMs). 7,8 Epiretinal membranes are characterized by the growth of fibrocellular tissue along the inner limiting membrane (ILM), which can lead to metamorphopsia and visual loss. The most frequently encountered, so-called idiopathic ERMs, are not linked to any other ocular disease process and their pathogenesis remains unidentified.…”

mentioning

confidence: 99%

Vitreal Cytokine Profile Differences Between Eyes With Epiretinal Membranes or Macular Holes

Zandi

Tappeiner

Pfister

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Cytokines play an important role in cell signaling in inflammatory and repair processes, also within the posterior segment of the eye. These molecules are thus implicated in the pathophysiology of several vitreoretinal diseases. In the present study, we compared vitreal cytokine profiles in patients with idiopathic epiretinal membranes (ERMs) and idiopathic full-thickness macular holes (MHs) without epiretinal membranes.METHODS. Native vitreal humor was collected during elective pars plana vitrectomy for the treatment of macular pathologies (group 1: ERM; group 2: MH) from patients without any other ocular or systemic disease. The concentrations of 43 chemokines and cytokines were measured in parallel by multiplex beads analysis. Intergroup comparisons were conducted using the Mann-Whitney U test and Bonferroni's correction, at a level of significance of P < 0.0012. RESULTS.Vitreal samples from 31 patients with ERMs (group 1) and from 30 with MHs (group 2) were analyzed. For 12 of the tested cytokines (GM-CSF, MCP-1, MIF, CCL15, CCL20, CCL17, CX3CL1, CXCL10, CXCL16, and TGF-b-1, -2, and -3), no intergroup differences were revealed; for the other 31, the concentrations were higher in the ERM than in the MH group (P < 0.0012 in each case).CONCLUSIONS. The vitreal levels of 72% of the tested cytokines were higher in ERM than in MH. This indicates that even in the absence of clinical markers, activation of inflammatory and profibrotic mechanisms is implicated in the progression of ERMs. Although frequently used as such in the past, eyes with ERMs should be considered with caution as a healthy control group.

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“…Previous studies revealed that retinal Müller glial cells are involved in the development and progression of ERM. 6,19,20 We also found GS(þ) Müller glial cells made up various proportions of the overall cell population, and part of these cells costained with Gli1. Müller glial cells can act as a source of proliferating progenitors to regenerate neurons in birds, 18 zebrafish, 21 and rodents, 22,23 and which can be activated by Shh signaling.…”

Section: Discussionmentioning

confidence: 51%

Gli1 Expression in Human Epiretinal Membranes

Baek

Lee

2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Jeon S, Baek J, Lee WK. Gli1 expression in human epiretinal membranes. Invest Ophthalmol Vis Sci. 2017;58:651-659. DOI:10.1167/ iovs.16-20409 PURPOSE. We evaluate the expression of Gli1 in human epiretinal membranes (ERM) and correlate this with clinical data. METHODS.We prospectively recruited patients with ERM. A total of 33 human ERM specimens were immunolabeled with anti-Gli1 antibody and the number of total cells/hyperfield (HF), Gli1(þ) cells/HF, and the percentage of Gli1(þ) cells/total cells were calculated. We evaluated the interrelationship of cellular properties and clinical findings, such as presence of diabetic retinopathy (DR), retinal breaks, intraocular inflammation, central foveal thickness, maximal retinal thickness, retinal contraction, lamellar holes, pseudoholes, the attenuation or absence of an inner segment/outer segment (IS/OS) junction/external limiting membrane (ELM), cystic changes, and paravascular inner retinal defects.RESULTS. Among 33 specimens, 25 specimens (75.8%) showed nuclear Gli1 expression. The mean Gli1(þ) cells/total cells was 54.0 6 36.7% (range, 0%-92.8%). There was significantly higher expression of Gli1(þ) cells in ERM specimens from patients with DR (P ¼ 0.014), and lower expression from patients with retinal breaks (P ¼ 0.022). Epiretinal membrane specimens from patients with alteration of IS/OS junction/ELM or cystic changes on OCT showed higher percentage of Gli1(þ) cells/total cells. CONCLUSIONS.Gli1 expression was detected in most ERM specimens. Patients who had DR or OCT findings indicating chronic retinal insults showed higher Gli1 expression. Gli1 may have a role in the pathogenesis of ERM after chronic retinal insults.

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Immunohistochemical Evaluation of Idiopathic Epiretinal Membranes and In Vitro Studies on the Effect of TGF-β on Müller Cells

Abstract: Type VI collagen and activated retinal Müller cells are present in iERM. Transforming growth factor-β1 induces an up-regulation of α-SMA stress fibers in retinal Müller cells and fibroblasts and appears to have a cell-specific effect on intracellular collagen expression.

Cited by 56 publications

References 43 publications

Pathologic Roles of Receptor-Associated Prorenin System in Idiopathic Epiretinal Membrane

Pathologic Roles of Receptor-Associated Prorenin System in Idiopathic Epiretinal Membrane

Vitreal Cytokine Profile Differences Between Eyes With Epiretinal Membranes or Macular Holes

Gli1 Expression in Human Epiretinal Membranes

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