Talk abstracts

Talk on Tuesday 03:45-04:00pm submitted by Isabella Palazzo

Reactive microglia and IL1β/IL-1R1-signaling mediate neuroprotection in excitotoxin-damaged mouse retina.

Isabella Palazzo, Levi Todd (Department of Neuroscience, College of Medicine, The Ohio State University), Lilianna Suarez, Warren A. Campbell (Department of Neuroscience, College of Medicine, The Ohio State University), Xiaoyu Liu, Ning Quan (Institute for Behavioral Medicine Research, College of Medicine, The Ohio State University), Leo Volkov (Department of Pathology and Immunology, Washington University School of Medicine), Thanh V. Hoang, Seth Blackshaw (Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine), Andy J. Fischer (Department of Neuroscience, College of Medicine, The Ohio State University)

Abstract:
Microglia and inflammatory signaling have context-dependent impacts on neuronal survival after CNS injury, and have been shown to influence astrocyte reactivity to mediate this effect. The role microglia play in regulating neuronal cell death after excitotoxic injury in the retina is not fully understood. This study investigates how microglia and the inflammatory mediator IL1β influence the survival of retinal neurons in response to excitotoxic damage.

NMDA-induced damage resulted in retinal neuron cell death, microglial reactivity, up-regulation of pro-inflammatory cytokines and genes associated with IL1β-signaling. Ablation of microglia resulted in elevated cell death and diminished neuronal survival in excitotoxin-damaged retinas. Exogenous IL1β treatment stimulated the reactivity of microglia in the absence of damage, reduced numbers of dying cells in damaged retinas, and increased neuronal survival following excitotoxic insult. IL1β signals through IL-1R1, which we found to be expressed in astrocytes, bipolar cells, endothelial cells and few Müller glia. IL1β failed to convey neuroprotection in an IL-1R1-null retina, but IL1β-mediated neuroprotection was rescued when expression of IL-1R1 was restored in astrocytes.

We conclude that reactive microglia provide protection to retinal neurons, since the absence of microglia is detrimental to survival. Additionally, IL1β promotes neuronal survival following excitotoxic injury and IL-1R1 expression is required. IL1R1 expression in astrocytes alone is sufficient for IL1β-mediated neuroprotection. Our data support the hypothesis that IL1β signaling through IL-1R1 in astrocytes conveys neuroprotection against excitotoxic retinal injury.

Keywords: microglia, neuroinflammation, astrocytes, retinal neuroprotection