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Endocrine

, Volume 65, Issue 3, pp 542–549 | Cite as

Activation of retinal Müller cells in response to glucose variability

  • Fabiana Picconi
  • Mariacristina Parravano
  • Francesca Sciarretta
  • Chiara Fulci
  • Michela Nali
  • Simona FrontoniEmail author
  • Monica Varano
  • Anna Maria Caccuri
Original Article
  • 86 Downloads

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.

Keywords

Glucose variability Müller cells activation Retinal neurodegeneration 

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

Notes

Acknowledgements

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

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

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.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Systems MedicineUniversity of Rome Tor VergataRomeItaly
  2. 2.Unit of Endocrinology, Diabetes and MetabolismS. Giovanni Calibita Fatebenefratelli HospitalRomeItaly
  3. 3.IRCCS-Fondazione BiettiRomeItaly
  4. 4.Department of Experimental MedicineUniversity of Rome Tor VergataRomeItaly
  5. 5.Center Nanoscience, Nanotechnology, Innovative Instrumentation (NAST)University of Rome Tor VergataRomeItaly

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