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Schmalen, A. ; Lorenz, L.* ; Grosche, A.* ; Pauly, D.* ; Deeg, C.A.* ; Hauck, S.M.

Proteomic phenotyping of stimulated Müller cells uncovers profound pro-inflammatory signaling and antigen-presenting capacity.

Front. Pharmacol. 12:771571 (2021)

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Müller cells are the main macroglial cells of the retina exerting a wealth of functions to maintain retinal homoeostasis. Upon pathological changes in the retina, they become gliotic with both protective and detrimental consequences. Accumulating data also provide evidence for a pivotal role of Müller cells in the pathogenesis of diabetic retinopathy (DR). While microglial cells, the resident immune cells of the retina are considered as main players in inflammatory processes associated with DR, the implication of activated Müller cells in chronic retinal inflammation remains to be elucidated. In order to assess the signaling capacity of Müller cells and their role in retinal inflammation, we performed in-depth proteomic analysis of Müller cell proteomes and secretomes after stimulation with INFγ, TNFα, IL-4, IL-6, IL-10, VEGF, TGFβ1, TGFβ2 and TGFβ3. We used both, primary porcine Müller cells and the human Müller cell line MIO-M1 for our hypothesis generating approach. Our results point towards an intense signaling capacity of Müller cells, which reacted in a highly discriminating manner upon treatment with different cytokines. Stimulation of Müller cells resulted in a primarily pro-inflammatory phenotype with secretion of cytokines and components of the complement system. Furthermore, we observed evidence for mitochondrial dysfunction, implying oxidative stress after treatment with the various cytokines. Finally, both MIO-M1 cells and primary porcine Müller cells showed several characteristics of atypical antigen-presenting cells, as they are capable of inducing MHC class I and MHC class II with co-stimulatory molecules. In line with this, they express proteins associated with formation and maturation of phagosomes. Thus, our findings underline the importance of Müller cell signaling in the inflamed retina, indicating an active role in chronic retinal inflammation.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Atypical Antigen-presenting Cell ; Complement System ; Cytokines ; Diabetic Retinopathy ; Immune Response ; Müller Cells ; Oxidative Phosphorylation ; Retina; Glial-cells; Transforming Growth-factor-beta-2; Mitochondrial Dysfunction; Diabetic-retinopathy; Oxidative Stress; Il-6 Production; Human Retina; Expression; Activation; Identification

ISSN (print) / ISBN 1663-9812

e-ISSN 1663-9812

Journal Frontiers in Pharmacology

Quellenangaben Volume: 12, Article Number: 771571

Publisher Frontiers

Publishing Place Lausanne

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) CF Metabolomics & Proteomics (CF-MPC)