Characteristics of Muller glial ce in MN-induced retinal degeneration

Retinal Muller glials have been shown to undergo reactive gliosis in a variety of retinal dise. Upregulation of glial fi brillary acidic protein (GFAP) is a hallmark of Muller 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 Muller cell activatio. Here, we investigated whether Muller cellfrom MNU-treated mice exhibit reactive gliosis. We found that Muller cells showed increased GFAP expression and increased membrane capacit, 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 Muller cell gliosis is characterized by plasma membrane increase without alteration in the membrane content of Kir channels. Taken together, our fi ndings show that Mller cells 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.