Human Idiopathic Epiretinal Membranes Express NGF and NGF Receptors

Minchiotti, Simona; Stampachiacchiere, Barbara; Micera, Alessandra; Lambìase, Alessandro; Ripandelli, Guido; Billi, Bernardo; Bombardieri, Stefano

doi:10.1097/iae.0b013e31815ec275

Cited by 41 publications

(31 citation statements)

References 23 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%

“…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%

“…Several cytokines and trophic factors were detected in iERM tissues and vitreous fluids, suggesting that the activation of signal transduction in glial cells by those molecules leads to iERM formation and progression48162122. FGF2, a member of a large family of neurotrophic molecules, supports survival and maturation of glial cells2125.…”

Section: Discussionmentioning

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%

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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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“…24,30 Transforming growth factor-b-1 and the nerve growth factor were shown to play a crucial role in fibroblast activities and were detected in the vitreal humor of each of the eight patients with idiopathic ERMs. 30 Kohno et al 25 demonstrated that TGF-b-2 stimulates the differentiation of hyalocytes into myofibroblasts. Interestingly, Zhao et al 31 reported hyalocytes and retinal Müller cells to be the predominant cell types in idiopathic ERMs.…”

Section: Discussionmentioning

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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“…This may be explained by tractional forces associated with ERM development and progression. 13 Contraction of the membrane exerts tangential traction on the inner retina and overlying vessels, making retinal vessels crowd toward the contraction center. 10 Thus, a smaller preoperative AUV may indicate more macular contraction caused by ERM.…”

Section: Eyementioning

confidence: 99%

Improvement of horizontal macular contraction after surgical removal of epiretinal membranes

Yang

Kim

Jung

et al. 2011

Eye

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Purpose To determine whether horizontal macular contraction caused by epiretinal membranes (ERMs) improves after surgical removal. Methods In this prospective, single-center, observational study, 63 consecutive patients with unilateral idiopathic ERM in one eye and no retinal disease in the fellow eye underwent pars plana vitrectomy. Fundus photography and optical coherence tomography (OCT) were performed preoperatively and at 3 months postoperatively. The area enclosed by superior and inferior major vessels from the optic disc to the fovea (area under major vessel (AUV)) and the macroscopic diverging angle (MDA) between superior and inferior major vessels were calculated using digital image analysis of fundus photographs and compared pre-and postoperatively. Results AUV was significantly smaller in the eyes with ERM compared with the normal fellow eyes (Po0.001). Significant postoperative change in AUV and MDA was demonstrated after ERM removal (Po0.001). However, postoperative AUV of grade 2 and 3 ERM eyes was still significantly smaller than that of normal fellow eyes. Macular thickness differences measured with stratus OCT were positively correlated with AUV differences. Conclusions Retinal topographic changes caused by ERM improved in part after ERM removal. The improvement of topographic changes were correlated with tomographic changes detected with OCT.

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Human Idiopathic Epiretinal Membranes Express NGF and NGF Receptors

Abstract: Idiopathic ERMs were characterized by myoFBs. The expression of NGF, trkA, and p75 in local myoFBs associated with changes in ERM vitreous NGF suggests an involvement of NGF, as previously reported for TGF-beta1, in the evolution and myoFB-mediated contractile activity of ERMs.

Cited by 41 publications

References 23 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

Improvement of horizontal macular contraction after surgical removal of epiretinal membranes

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