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Updated: Sep 30, 2026
Characterization of a Novel Human Organotypic Retinal Culture Technique
Published on: June 9, 2021
Membrane conductance of Müller glial cells in proliferative diabetic retinopathy
Andreas Bringmann1, Thomas Pannicke, Susanne Uhlmann
1Department of Neurophysiology, Paul Flechsig Institute of Brain Research, University of Leipzig, Germany. bria@medizin.uni-leipzig.de
Background:
It is not known whether the membrane features of human Müller cells are altered in proliferative diabetic retinopathy (PDR). We performed a study to investigate the expression of several distinct forms of membrane conductance in Müller glial cells from a patient with PDR compared to cells from healthy donors (control cells).
Methods:
Müller cells were isolated 2 hours after vitreoretinal surgery in the case of the patient and within 24 hours in the case of the autopsy eyes. Whole-cell voltage-clamp recordings were made. The results for the two groups were compared with the Mann-Whitney U test.
Results:
As assayed by the whole-cell membrane capacitance, the cells from the patient with PDR showed hypertrophy in comparison to the control cells (mean 85.1 pF [standard deviation (SD) 19.7 pF] vs. 54.3 pF [SD 13.8 pF]). The cells from the patient displayed strong downregulation of inwardly rectifying potassium ion (Kir) currents (mean 0.41 [SD 0.24] pA/pF, compared to 3.43 [SD 1.86] pA/pF for the control cells). The Kir current downregulation was accompanied by a less negative membrane potential (-57.3 mV [SD 16.9 mV], compared with -82.3 mV [SD 5.3 mV] for the control cells). Both the number and the amplitude of voltage-gated sodium ion currents were enhanced in cells from the patient. When P2X7 receptors were activated by 2'-/3'-O-(4-benzoylbenzoyl)-adenosine triphosphate, cells in both groups displayed opening of a cation conductance and, simultaneously, an increase in currents through calcium ion-activated potassium ion channels.
Interpretation:
Changes in Müller cell membrane conductance in PDR are similar to those described in proliferative vitreoretinopathy. The down-regulation of active Kir channels and the membrane depolarization likely disturb voltage-dependent Müller cell functions, such as regulation of local ion concentrations and uptake of neurotransmitters. The enhanced entry of calcium ions from the extracellular space and the subsequent stimulation of calcium-activated potassium channels support Müller cell proliferation in PDR.
Insights
Müller cells in proliferative diabetic retinopathy (PDR) show hypertrophy and altered membrane currents, specifically reduced inwardly rectifying potassium ion (Kir) currents. These changes likely disrupt Müller cell functions and promote PDR progression.
Area of Science:
- Ophthalmology
- Neuroscience
- Cell Biology
Background:
- Proliferative diabetic retinopathy (PDR) is a major cause of vision loss.
- Müller glial cells play critical roles in retinal function and homeostasis.
- The impact of PDR on Müller cell membrane properties remains largely unknown.
Purpose of the Study:
- To investigate alterations in membrane conductance of human Müller cells in PDR.
- To compare membrane properties of Müller cells from PDR patients with those from healthy donors.
Main Methods:
- Isolation of human Müller cells from PDR patients and healthy donors.
- Whole-cell voltage-clamp recordings to assess membrane currents.
- Statistical comparison using the Mann-Whitney U test.
Main Results:
- Müller cells from PDR patients exhibited hypertrophy (increased membrane capacitance).
- Significant downregulation of inwardly rectifying potassium ion (Kir) currents was observed in PDR cells.
- PDR cells showed membrane depolarization and enhanced voltage-gated sodium ion currents.
- Activation of P2X7 receptors induced cation conductance and calcium-activated potassium currents in both groups.
Conclusions:
- PDR induces changes in Müller cell membrane conductance, similar to proliferative vitreoretinopathy.
- Downregulation of Kir currents and membrane depolarization impair Müller cell functions.
- Enhanced calcium influx and calcium-activated potassium channel activity may contribute to Müller cell proliferation in PDR.
