Single-Cell Protein and Transcriptional Characterization of Epiretinal Membranes From Patients With Proliferative Vitreoretinopathy
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Single-Cell Protein and Transcriptional Characterization of Epiretinal Membranes From Patients With Proliferative Vitreoretinopathy. / Laich, Yannik; Wolf, Julian; Hajdu, Rozina Ida; Schlecht, Anja; Bucher, Felicitas; Pauleikhoff, Laurenz; Busch, Martin; Martin, Gottfried; Faatz, Henrik; Killmer, Saskia; Bengsch, Bertram; Stahl, Andreas; Lommatzsch, Albrecht; Schlunck, Günther; Agostini, Hansjürgen; Boneva, Stefaniya; Lange, Clemens.
in: INVEST OPHTH VIS SCI, Jahrgang 63, Nr. 5, 02.05.2022, S. 17.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Single-Cell Protein and Transcriptional Characterization of Epiretinal Membranes From Patients With Proliferative Vitreoretinopathy
AU - Laich, Yannik
AU - Wolf, Julian
AU - Hajdu, Rozina Ida
AU - Schlecht, Anja
AU - Bucher, Felicitas
AU - Pauleikhoff, Laurenz
AU - Busch, Martin
AU - Martin, Gottfried
AU - Faatz, Henrik
AU - Killmer, Saskia
AU - Bengsch, Bertram
AU - Stahl, Andreas
AU - Lommatzsch, Albrecht
AU - Schlunck, Günther
AU - Agostini, Hansjürgen
AU - Boneva, Stefaniya
AU - Lange, Clemens
PY - 2022/5/2
Y1 - 2022/5/2
N2 - PURPOSE: 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.METHODS: A 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.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 α-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.CONCLUSIONS: Epiretinal 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.
AB - PURPOSE: 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.METHODS: A 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.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 α-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.CONCLUSIONS: Epiretinal 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.
KW - Epiretinal Membrane/metabolism
KW - Humans
KW - RNA/genetics
KW - Retina/metabolism
KW - Retinal Pigment Epithelium/metabolism
KW - Vitreoretinopathy, Proliferative/metabolism
U2 - 10.1167/iovs.63.5.17
DO - 10.1167/iovs.63.5.17
M3 - SCORING: Journal article
C2 - 35579905
VL - 63
SP - 17
JO - INVEST OPHTH VIS SCI
JF - INVEST OPHTH VIS SCI
SN - 0146-0404
IS - 5
ER -
