Activation of retinal Müller cells in response to glucose variability
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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.
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).
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.
Our results highlight Müller cells activation in response to glucose variability and a different susceptibility depending on the basal glucose conditions.
KeywordsGlucose variability Müller cells activation Retinal neurodegeneration
glial fibrillary acidic protein
retinal Müller cells
phospho-active extracellular signal-regulated kinase
retinal ganglion cells
- N cells
5 mM (1 g/L) glucose
- H cells
25 mM (4.5 g/L) glucose
glucagon-like peptide 1 receptor agonists
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.
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 was obtained from all individual participants included in the study.
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