{
    "abstract": "Proliferative vitreoretinopathy (PVR) remains an unresolved clinical challenge and can lead to frequent revision surgery and blindness vision loss. The aim of this study was to characterize the microenvironment of epiretinal PVR tissue, in order to shed more light on the complex pathophysiology and to unravel new treatment options.\nA total of 44 tissue samples were analyzed in this study, including 19 epiretinal PVRs, 13 epiretinal membranes (ERMs) from patients with macular pucker, as well as 12 internal limiting membranes (ILMs). The cellular and molecular microenvironment was assessed by cell type deconvolution analysis (xCell), RNA sequencing data and single-cell imaging mass cytometry. Candidate drugs for PVR treatment were identified in silico via a transcriptome-based drug-repurposing approach.\nRNA sequencing of tissue samples demonstrated distinct transcriptional profiles of PVR, ERM, and ILM samples. Differential gene expression analysis revealed 3194 upregulated genes in PVR compared with ILM, including FN1 and SPARC, which contribute to biological processes, such as extracellular matrix (ECM) organization. The xCell and IMC analyses showed that PVR membranes were composed of macrophages, retinal pigment epithelium, and \u03b1-SMA-positive myofibroblasts, the latter predominantly characterized by the co-expression of immune cell signature markers. Finally, 13 drugs were identified as potential therapeutics for PVR, including aminocaproic acid and various topoisomerase-2A inhibitors.\nEpiretinal PVR membranes exhibit a unique and complex transcriptional and cellular profile dominated by immune cells and myofibroblasts, as well as a variety of ECM components. Our findings provide new insights into the pathophysiology of PVR and suggest potential targeted therapeutic options.",
    "authors": [
        {
            "affiliation": "Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.",
            "firstname": "Yannik",
            "initials": "Y",
            "lastname": "Laich"
        },
        {
            "affiliation": "Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.",
            "firstname": "Julian",
            "initials": "J",
            "lastname": "Wolf"
        },
        {
            "affiliation": "Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.\nDepartment of Ophthalmology, Semmelweis University, Budapest, Hungary.",
            "firstname": "Rozina Ida",
            "initials": "RI",
            "lastname": "Hajdu"
        },
        {
            "affiliation": "Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.\nInstitute of Anatomy and Cell Biology, Julius Maximilian University Wuerzburg, Wuerzburg, Germany.",
            "firstname": "Anja",
            "initials": "A",
            "lastname": "Schlecht"
        },
        {
            "affiliation": "Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.",
            "firstname": "Felicitas",
            "initials": "F",
            "lastname": "Bucher"
        },
        {
            "affiliation": "Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.",
            "firstname": "Laurenz",
            "initials": "L",
            "lastname": "Pauleikhoff"
        },
        {
            "affiliation": "Department of Ophthalmology, University Medical Center Greifswald, Greifswald, Germany.",
            "firstname": "Martin",
            "initials": "M",
            "lastname": "Busch"
        },
        {
            "affiliation": "Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.",
            "firstname": "Gottfried",
            "initials": "G",
            "lastname": "Martin"
        },
        {
            "affiliation": "Achim Wessing Institute for Imaging in Ophthalmology, University Hospital Essen, Essen, Germany.\nOphtha-Lab, Department of Ophthalmology at St. Franziskus Hospital, Muenster, Germany.",
            "firstname": "Henrik",
            "initials": "H",
            "lastname": "Faatz"
        },
        {
            "affiliation": "Department of Medicine II (Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.",
            "firstname": "Saskia",
            "initials": "S",
            "lastname": "Killmer"
        },
        {
            "affiliation": "Department of Medicine II (Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases), Freiburg University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.\nSignaling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.",
            "firstname": "Bertram",
            "initials": "B",
            "lastname": "Bengsch"
        },
        {
            "affiliation": "Department of Ophthalmology, University Medical Center Greifswald, Greifswald, Germany.",
            "firstname": "Andreas",
            "initials": "A",
            "lastname": "Stahl"
        },
        {
            "affiliation": "Achim Wessing Institute for Imaging in Ophthalmology, University Hospital Essen, Essen, Germany.\nOphtha-Lab, Department of Ophthalmology at St. Franziskus Hospital, Muenster, Germany.",
            "firstname": "Albrecht",
            "initials": "A",
            "lastname": "Lommatzsch"
        },
        {
            "affiliation": "Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.",
            "firstname": "G\u00fcnther",
            "initials": "G",
            "lastname": "Schlunck"
        },
        {
            "affiliation": "Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.",
            "firstname": "Hansj\u00fcrgen",
            "initials": "H",
            "lastname": "Agostini"
        },
        {
            "affiliation": "Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.",
            "firstname": "Stefaniya",
            "initials": "S",
            "lastname": "Boneva"
        },
        {
            "affiliation": "Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.\nOphtha-Lab, Department of Ophthalmology at St. Franziskus Hospital, Muenster, Germany.",
            "firstname": "Clemens",
            "initials": "C",
            "lastname": "Lange"
        }
    ],
    "conclusions": null,
    "copyrights": null,
    "doi": "10.1167/iovs.63.5.17",
    "journal": "Investigative ophthalmology & visual science",
    "keywords": [],
    "methods": null,
    "publication_date": "2022-05-18",
    "pubmed_id": "35579905\n1867299\n12101443\n30585928\n9780100\n32666172\n1420061\n30597308\n16679807\n32150307\n33585455\n34795670\n32479607\n33042148\n32339498\n23104886\n24227677\n31691826\n25516281\n27207943\n22455463\n29141660\n22872506\n32194980\n21849665\n30476243\n29126136\n17008526\n16199517\n34544377\n30713109\n17076895\n28783155\n26095251\n31780669\n34477966\n26719706\n22942638\n28391660\n15945009\n2378854\n27798121\n10892881\n4038135\n23935989\n9700173\n28714933\n26410397\n29921749\n18161745\n20528783\n27906172\n9330849\n1397126\n18228032\n31429189\n15869763\n28612231\n22491400\n17341145\n9624252\n20860474\n28777835\n34462712\n31179399",
    "results": "RNA sequencing of tissue samples demonstrated distinct transcriptional profiles of PVR, ERM, and ILM samples. Differential gene expression analysis revealed 3194 upregulated genes in PVR compared with ILM, including FN1 and SPARC, which contribute to biological processes, such as extracellular matrix (ECM) organization. The xCell and IMC analyses showed that PVR membranes were composed of macrophages, retinal pigment epithelium, and \u03b1-SMA-positive myofibroblasts, the latter predominantly characterized by the co-expression of immune cell signature markers. Finally, 13 drugs were identified as potential therapeutics for PVR, including aminocaproic acid and various topoisomerase-2A inhibitors.",
    "title": "Single-Cell Protein and Transcriptional Characterization of Epiretinal Membranes From Patients With Proliferative Vitreoretinopathy.",
    "xml": "<Element 'PubmedArticle' at 0x788506aae840>"
}