Activation of retinal Müller cells in response to glucose variability

Fabiana Picconi, Mariacristina Parravano, Francesca Sciarretta, Chiara Fulci, Michela Nali, Simona Frontoni, Monica Varano, Anna Maria Caccuri

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)542-549
Number of pages8
JournalEndocrine
Volume65
Issue number3
DOIs
Publication statusPublished - Sep 1 2019

Keywords

  • Glucose variability
  • Müller cells activation
  • Retinal neurodegeneration

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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