Role of the Intravitreal Growth Factors in the Pathogenesis of Idiopathic Epiretinal Membrane

Iannetti, Ludovico; Accorinti, Massimo; Malagola, R; Bozzoni-Pantaleoni, Francesco; Dalt, Stefano Da; Nicoletti, Ferdinando; Gradini, Roberto; Traficante, Anna; Campanella, Michelangelo; Pivetti-Pezzi, Paola

doi:10.1167/iovs.10-7116

Cited by 53 publications

(56 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Transforming growth factor-b-2 thus appears to be an important growth factor in the evolution of ERMs and in their contraction. 25,32 In our study, the vitreal levels of TGF-b-2 in the ERM group were higher than those of TGF-b-1 and -3. However, such was the case also in the MH group, which is a seemingly unaccountable finding.…”

Section: Discussionmentioning

confidence: 40%

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

Zandi

Tappeiner

Pfister

et al. 2016

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 40%

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

Zandi

Tappeiner

Pfister

et al. 2016

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

show abstract

“…GDNF, a member of the TGF-β-related neurotrophic factor family, increases FGF2 production in glial cells25. NGF and TGF-β1 have been reported to stimulate glial cells to transdifferentiate into myofibroblasts1622. Our current data showed that the expression of these fibrosis-related molecules in iERM were governed by RAPS-mediated mechanisms (Fig.…”

Section: Discussionmentioning

confidence: 50%

“…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. Stimulation of fibroblasts with Ang II are known to promote collagen synthesis24; however, little is known about whether this is the case with Müller glial cells.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

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

Dong

Kanda

Noda

et al. 2017

Sci Rep

View full text Add to dashboard Cite

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.

show abstract

“…Furthermore, an incomplete PVD might provide appropriate conditions for fibrocellular proliferation in the area between the vitreous and the retina [7]. In the process of ERM formation, extracellular matrix, cytokines and growth factors are involved in cellular signal transmission and in tissue changes [8]. …”

Section: Introductionmentioning

confidence: 99%

miRNAs in the vitreous humor of patients affected by idiopathic epiretinal membrane and macular hole

et al. 2017

View full text Add to dashboard Cite

PurposeThe aim of the present study was to assess the expression of miRNAs in the Vitreous Humor (VH) of patients with Macular Hole (MH) and Epiretinal Membrane (ERM) compared to a control group.MethodsIn this prospective, comparative study, 2-ml of VH was extracted from the core of the vitreous chamber in consecutive patients who underwent standard vitrectomy for ERM and MH. RNA was extracted and TaqMan® Low Density Arrays (TLDAs) were used to profile the transcriptome of 754 miRNAs. Results were validated by single TaqMan® assays. Finally, we created a biological network of differentially expressed miRNA targets and their nearest neighbors.ResultsOverall 10 eyes with MH, 16 eyes with idiopathic ERM and 6 controls were enrolled in the study. Profiling data identified 5 miRNAs differentially expressed in patients affected by MH and ERM with respect to controls. Four were downregulated (miR-19b, miR-24, miR-155, miR-451) and 1 was downregulated (miR-29a); TaqMan® assays of the VH of patients affected by MH and ERM, with respect to controls, showed that the most differentially expressed were miR-19b (FC -9.13, p:<0.00004), mir-24 (FC -7.52, p:<0.004) and miR-142-3p (FC -5.32, p:<0.011). Our network data showed that deregulation of differentially expressed miRNAs induces an alteration of several pathways associated with genes involved in both MH and ERM.ConclusionThe present study suggests that disregulation of miR-19b, miR-24 and miR-142-3p, might be related to the alterations that characterize patients affected by MH and ERM.

show abstract

Role of the Intravitreal Growth Factors in the Pathogenesis of Idiopathic Epiretinal Membrane

Abstract: The present study reveals that TGFβ2 and NGF are associated with idiopathic ERMs, suggesting a novel compensatory mechanism so far never proposed.

Cited by 53 publications

References 19 publications

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

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

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

miRNAs in the vitreous humor of patients affected by idiopathic epiretinal membrane and macular hole

Contact Info

Product

Resources

About