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Activation of retinal Müller cells in response to glucose variability

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Abstract

Purpose

In the earliest stages of diabetic retinopathy (DR), a dysfunction of Müller cells, characterized by high levels of glial fibrillary acidic protein (GFAP), and aquaporins (AQP), has been observed. Although chronic hyperglycemia causes the activation of Müller cells, the effect of glycemic fluctuations is yet unknown. The aim of the study was to analyze the impact of glucose variability on rat retinal Müller cells (rMC-1) adapted to either normal (5 mM) or high (25 mM) glucose levels.

Methods

rMC-1 were cultured in a medium containing either 5 mM (N cells) or 25 mM of glucose (H cells) and then incubated for 96 h in a medium containing (a) low glucose (either 1–3 or 5 mM), (b) basal glucose (either 5 or 25 mM), (c) high glucose (either 25 or 45 mM), (d) basal and high glucose alternated every 24 h; (e) low- and high glucose alternated every 24 h; (f) basal glucose with episodes of low glucose for 30 min twice a day. Müller cells activation was evaluated by measuring the levels of GFAP, AQP4, and phospho-active extracellular signal-regulated kinase (pERK).

Results

Under both basal and high glucose concentrations rMC-1 were viable, but their response to glucose excursions was different. In N cells kept under normal (5 mM) glucose, a significant glial activation was measured not only in response to constant high glucose but also to alternating low/high glucose. In H cells, adapted to 25 mM glucose, a significant response was observed only after exposition to a lower (5 mM) glucose concentration.

Conclusion

Our results highlight Müller cells activation in response to glucose variability and a different susceptibility depending on the basal glucose conditions.

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Abbreviations

DR:

diabetic retinopathy

GFAP:

glial fibrillary acidic protein

AQP:

aquaporin

rMC-1:

retinal Müller cells

pERK:

phospho-active extracellular signal-regulated kinase

RGC:

retinal ganglion cells

N cells:

5 mM (1 g/L) glucose

H cells:

25 mM (4.5 g/L) glucose

GLUT1:

glucose transporter-1

GLP-1RA:

glucagon-like peptide 1 receptor agonists

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Acknowledgements

The research for this paper was partially supported by the Italian Ministry of Health and Fondazione Roma.

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Authors and Affiliations

  1. Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy

    Fabiana Picconi & Simona Frontoni

  2. Unit of Endocrinology, Diabetes and Metabolism, S. Giovanni Calibita Fatebenefratelli Hospital, Rome, Italy

    Fabiana Picconi & Simona Frontoni

  3. IRCCS-Fondazione Bietti, Rome, Italy

    Mariacristina Parravano & Monica Varano

  4. Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy

    Francesca Sciarretta, Chiara Fulci, Michela Nali & Anna Maria Caccuri

  5. Center Nanoscience, Nanotechnology, Innovative Instrumentation (NAST), University of Rome Tor Vergata, Rome, Italy

    Anna Maria Caccuri

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  1. Fabiana Picconi
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Correspondence to Simona Frontoni.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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These authors contributed equally: Fabiana Picconi, Mariacristina Parravano

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Picconi, F., Parravano, M., Sciarretta, F. et al. Activation of retinal Müller cells in response to glucose variability. Endocrine 65, 542–549 (2019). https://doi.org/10.1007/s12020-019-02017-5

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