Related Experiment Videos
Characteristics of Müller glial cells in MNU-induced retinal degeneration
Miriam Reisenhofer1, Thomas Pannicke2, Andreas Reichenbach2
1Department of Ophthalmology,Inselspital,Bern University Hospital,University of Bern,3010 Bern,Switzerland.
Abstract:
Retinal Müller glial cells have been shown to undergo reactive gliosis in a variety of retinal diseases. Upregulation of glial fibrillary acidic protein (GFAP) is a hallmark of Müller cell activation. Reactive gliosis after retinal detachment or ischemia/reperfusion is characterized by hypertrophy and downregulation of inwardly rectifying K+ (Kir) currents. However, this kind of physiological alteration could not be detected in slowly progressing retinal degenerations. The photoreceptor toxin N-methyl-N-nitrosourea (MNU) leads to the rapid loss of cells in the outer nuclear layer and subsequent Müller cell activation. Here, we investigated whether Müller cells from MNU-treated mice exhibit reactive gliosis. We found that Müller cells showed increased GFAP expression and increased membrane capacitance, indicating hypertrophy. Membrane potential and Kir channel-mediated K+ currents were not significantly altered whereas Kir4.1 mRNA expression and Kir-mediated inward current densities were markedly decreased. This suggests that MNU-induced Müller cell gliosis is characterized by plasma membrane increase without alteration in the membrane content of Kir channels. Taken together, our findings show that Müller cells of MNU-treated mice are reactive and respond with a form of gliosis which is characterized by cellular hypertrophy but no changes in Kir current amplitudes.
Insights
Müller glial cells in N-methyl-N-nitrosourea (MNU) treated mice show reactive gliosis, characterized by cell hypertrophy and decreased Kir4.1 mRNA. This retinal degeneration model reveals a unique form of Müller cell activation without altered Kir current amplitudes.
Area of Science:
- Neuroscience
- Ophthalmology
- Cell Biology
Background:
- Retinal Müller glial cells activate during disease via reactive gliosis.
- Glial fibrillary acidic protein (GFAP) upregulation marks Müller cell activation.
- Reactive gliosis in retinal detachment/ischemia involves hypertrophy and reduced inwardly rectifying K+ (Kir) currents.
Purpose of the Study:
- To investigate Müller cell reactive gliosis in a mouse model of rapid photoreceptor degeneration induced by N-methyl-N-nitrosourea (MNU).
- To determine if MNU-induced Müller cell activation alters membrane potential, Kir currents, or Kir4.1 expression.
Main Methods:
- Treatment of mice with the photoreceptor toxin N-methyl-N-nitrosourea (MNU).
- Assessment of Müller cell hypertrophy via increased membrane capacitance and GFAP expression.
- Electrophysiological recordings to measure membrane potential and Kir currents.
- Quantitative analysis of Kir4.1 mRNA expression.
Main Results:
- MNU-induced Müller cells exhibited increased GFAP expression and membrane capacitance, indicating hypertrophy.
- No significant alterations were observed in membrane potential or Kir channel-mediated K+ currents.
- Kir4.1 mRNA expression and Kir-mediated inward current densities were markedly decreased.
- MNU-induced gliosis is characterized by plasma membrane increase without changes in membrane Kir channel content.
Conclusions:
- Müller cells in MNU-treated mice display reactive gliosis.
- This reactive gliosis involves cellular hypertrophy but not alterations in Kir current amplitudes.
- MNU-induced retinal degeneration provides a model for studying Müller cell hypertrophy independent of Kir current changes.