High glucose treatment promotes extracellular matrix proteome remodeling in Müller glial cells

Sagmeister, Sandra; Merl-Pham, Juliane; Petrera, Agnese; Deeg, Cornelia A.; Hauck, Stefanie M.

doi:10.7717/peerj.11316

Cited by 5 publications

(4 citation statements)

References 69 publications

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“…Our data confirm that Müller cells are crucially involved in immunological processes in the retina as well, as they possess an antigen processing and presenting machinery and secrete proinflammatory cytokines (Karlstetter et al, 2015). We have previously shown that the cultivation of primary porcine Müller cells under hyperglycemic conditions resulted in higher expression levels of MHC class II molecules, pointing towards an immunologically activated state of Müller cells in DR (Sagmeister et al, 2021).…”

Section: Discussionsupporting

confidence: 80%

“…No experimental animals were involved in this study. Within 2 h after enucleation, eyes were processed under a laminar flow hood under sterile conditions as previously described (Lorenz et al, 2021b;Sagmeister et al, 2021). In short, periocular tissue was removed and the eyeballs were rinsed in 80% ethanol followed by washing with cold PBS.…”

Section: Cell Preparation and Culturementioning

confidence: 99%

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Proteomic Phenotyping of Stimulated Müller Cells Uncovers Profound Pro-Inflammatory Signaling and Antigen-Presenting Capacity

Schmalen

Lorenz²,

Grosche³

et al. 2021

Front. Pharmacol.

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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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Section: Discussionsupporting

confidence: 80%

Section: Cell Preparation and Culturementioning

confidence: 99%

Proteomic Phenotyping of Stimulated Müller Cells Uncovers Profound Pro-Inflammatory Signaling and Antigen-Presenting Capacity

Schmalen

Lorenz²,

Grosche³

et al. 2021

Front. Pharmacol.

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show abstract

Section: Discussionsupporting

confidence: 80%

Section: Cell Preparation and Culturementioning

confidence: 99%

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Single-cell transcriptomics reveals the molecular basis of human iPS cell differentiation into ectodermal ocular lineages

Howard,

Ishikawa,

Katayama

et al. 2024

Commun Biol

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The generation of a self-formed, ectodermal, autonomous multi-zone (SEAM) from human induced pluripotent stem cells (hiPSCs) offers a unique perspective to study the dynamics of ocular cell differentiation over time. Here, by utilising single-cell transcriptomics, we have (i) identified, (ii) molecularly characterised and (iii) ascertained the developmental trajectories of ectodermally-derived ocular cell populations which emerge within SEAMs as they form. Our analysis reveals interdependency between tissues of the early eye and delineates the sequential formation and maturation of distinct cell types over a 12-week period. We demonstrate a progression from pluripotency through to tissue specification and differentiation which encompasses both surface ectodermal and neuroectodermal ocular lineages and the generation of iPSC-derived components of the developing cornea, conjunctiva, lens, and retina. Our findings not only advance the understanding of ocular development in a stem cell-based system of human origin, but also establish a robust methodological paradigm for exploring cellular and molecular dynamics during SEAM formation at single-cell resolution and highlight the potential of hiPSC-derived systems as powerful platforms for modelling human eye development and disease.

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High glucose treatment promotes extracellular matrix proteome remodeling in Müller glial cells

Cited by 5 publications

References 69 publications

Proteomic Phenotyping of Stimulated Müller Cells Uncovers Profound Pro-Inflammatory Signaling and Antigen-Presenting Capacity

Proteomic Phenotyping of Stimulated Müller Cells Uncovers Profound Pro-Inflammatory Signaling and Antigen-Presenting Capacity

DataSheet2.xlsx

Single-cell transcriptomics reveals the molecular basis of human iPS cell differentiation into ectodermal ocular lineages

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