Role of Müller cells in the onset and progression of neuronal degeneration after acute retinal ischemia

Schultz, Rowena GND

Müller cells (MCs), the most common retinal glial cell type, are responsible for the maintenance of retinal homeostasis under physiological conditions. After retinal damage, MCs become reactive and protect and support the neurons. However, this reactivity can lead to loss of basal functions and thus to impaired tissue homeostasis. The effect and timing of this "double faced" behavior of reactive glial cells has not been fully elucidated. The aim of this study was to investigate the time point for the transition of MC gliosis from neuroprotective to detrimental, and to investigate the effect of enhanced antioxidant activity of these cells on neuronal survival in vivo in a mouse model of acute ischemic/reperfusion injury. Fluorocitrate was injected into the vitreous of the eye to study the timing of gliosis. This led to a specific inhibition of the Krebs cycle in MCs and thus to a reduced cell metabolism. This transient inhibition allowed the identification of three phases of the gliotic cell response: an early neuroprotective phase, followed by the transition to a later deleterious phase beginning 12-18 hours after ischemia. One hallmark of ischemia is the increase in oxidative stress. Selective enhancement of MCs antioxidative response through overexpression of the mitochondrial enzyme frataxin resulted in increased neuronal survival. This correlated with increased expression of antioxidant enzymes and neurotrophic factors. Thus, a time-dependent influence or a functional support of MCs can increase the neuronal survival after retinal injuries. This is associated with decreased neuron-detrimental gliosis and enhancement of intrinsic protective mechanisms. This makes MCs a lucrative therapeutic target for treatment of ischemic retinal pathologies.

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Schultz, Rowena: Role of Müller cells in the onset and progression of neuronal degeneration after acute retinal ischemia. Jena 2018.

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