Gene expression analysis identifies two distinct molecular clusters of idiopatic epiretinal membranes

Coltrini, Daniela; Belleri, Mirella; Gambicorti, Elena; Romano, Davide; Morescalchi, Francesco; Chandran, Adwaid Manu Krishna; Calza, Stefano; Semeraro, Francesco; Presta, Marco

doi:10.1016/j.bbadis.2020.165938

Cited by 12 publications

(12 citation statements)

References 54 publications

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“…Because of the small size and limited material availability, few studies concerning the cell compositions of FVMs have been reported. Daniela et al (40) recently reported using RT-qPCR analysis to identify two distinct idiopathic epiretinal membrane clusters based on 20 selected genes. However, the cellular heterogeneity of cell components in disease-specific FVMs and in-depth intercellular interactions cannot be fully explored.…”

Section: Discussionmentioning

confidence: 99%

Single-Cell Transcriptomics Reveals Novel Role of Microglia in Fibrovascular Membrane of Proliferative Diabetic Retinopathy

Mao

Chen

et al. 2022

Diabetes

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Vitreous fibrovascular membranes (FVMs), the hallmark of proliferative diabetic retinopathy (PDR), cause retinal hemorrhage, detachment and eventually blindness. However, little is known about the pathophysiology of FVM. In this study, we employed single-cell RNA sequencing on surgically harvested PDR-FVMs and generated a comprehensive cell atlas of FVM. A total of 8 cellular compositions were identified, with microglia as the major cell population. We identified a GPNMB+ subpopulation of microglia, which presented both profibrotic and fibrogenic properties. Pseudotime analysis further revealed the profibrotic microglia was uniquely differentiated from retina-resident microglia and expanded in PDR setting. Ligand-receptor interactions between the profibrotic microglia and cytokines upregulated in PDR vitreous implicated the involvement of several pathways, including CCR5, IFNGR1 and CD44 signaling, in the microglial activation within PDR microenvironment. Collectively, our description of the novel microglia phenotypes in PDR-FVM may offer new insight into the cellular and molecular mechanism underlying the pathogenesis of DR, as well as potential signaling pathways amenable to disease-specific intervention.

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Section: Discussionmentioning

confidence: 99%

Single-Cell Transcriptomics Reveals Novel Role of Microglia in Fibrovascular Membrane of Proliferative Diabetic Retinopathy

Mao

Chen

et al. 2022

Diabetes

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“…A recent study by Coltrini and colleagues looked at RNA isolated from the cells present in iERMs obtained by "membrane peeling" from 56 patients [222]. The iERMs were staged clinically and assigned scores of A or B, with a score of B given to iERMs that were thicker and more easily visualized due to vascularization and pigmentation from de-differentiated RPE cells.…”

Section: Vitreoretinopathy (Pvr)mentioning

confidence: 99%

Immune responses to injury and their links to eye disease

Stepp

Menko

2021

Translational Research

112

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…However, some investigators also observed a certain number of iERMs apparently lacking collagen I [ 18 , 19 ]. Proteomic profiling confirmed the presence of α1(I) and α2(I) collagen chains [ 13 ], and gene expression analysis showed that COL1A1 gene is expressed by iERM cells [ 25 , 26 ]. Though with some restraints, an attempt to characterize cells responsible for collagen I deposition has recently taken place by confocal microscopy with the identification of glial fibrillary acid protein (GFAP) - /vimentin + /αSMA + /heat shock protein 90 + myofibroblast-like cells with collagen I-immunoreactive intracytoplasmic bodies [ 12 ].…”

Section: Ecm Components Of Iermsmentioning

confidence: 99%

“…However, the distribution of the two collagens does not match perfectly as immunoreactive areas for just one of the two collagens are also present [ 21 ]. Whereas proteomic profiling of iERMs has not confirmed the presence of collagen VI [ 13 ], gene expression analysis did find COL6A1 mRNA [ 26 ].…”

Section: Ecm Components Of Iermsmentioning

confidence: 99%

Untangling the Extracellular Matrix of Idiopathic Epiretinal Membrane: A Path Winding among Structure, Interactomics and Translational Medicine

Bianchi

Altera

Barone

et al. 2022

Cells

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Idiopathic epiretinal membranes (iERMs) are fibrocellular sheets of tissue that develop at the vitreoretinal interface. The iERMs consist of cells and an extracellular matrix (ECM) formed by a complex array of structural proteins and a large number of proteins that regulate cell–matrix interaction, matrix deposition and remodelling. Many components of the ECM tend to produce a layered pattern that can influence the tractional properties of the membranes. We applied a bioinformatics approach on a list of proteins previously identified with an MS-based proteomic analysis on samples of iERM to report the interactome of some key proteins. The performed pathway analysis highlights interactions occurring among ECM molecules, their cell receptors and intra- or extracellular proteins that may play a role in matrix biology in this special context. In particular, integrin β1, cathepsin B, epidermal growth factor receptor, protein-glutamine gamma-glutamyltransferase 2 and prolow-density lipoprotein receptor-related protein 1 are key hubs in the outlined protein–protein cross-talks. A section on the biomarkers that can be found in the vitreous humor of patients affected by iERM and that can modulate matrix deposition is also presented. Finally, translational medicine in iERM treatment has been summed up taking stock of the techniques that have been proposed for pharmacologic vitreolysis.

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Gene expression analysis identifies two distinct molecular clusters of idiopatic epiretinal membranes

Cited by 12 publications

References 54 publications

Single-Cell Transcriptomics Reveals Novel Role of Microglia in Fibrovascular Membrane of Proliferative Diabetic Retinopathy

Single-Cell Transcriptomics Reveals Novel Role of Microglia in Fibrovascular Membrane of Proliferative Diabetic Retinopathy

Immune responses to injury and their links to eye disease

Untangling the Extracellular Matrix of Idiopathic Epiretinal Membrane: A Path Winding among Structure, Interactomics and Translational Medicine

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