E 02 INF - β signaling and microglial activation in retinal degeneration

Microglial activation is a hallmark of human retinal degenerations including Retinitis Pigmentosa and Age-related Macular Degeneration (AMD) [1]. Genetic mouse models have shown that chronic alerted microglia trigger and perpetuate retinal degeneration leading to vision loss [2-3]. Immuno-regulatory microglia exist in the early activation phase but are overwhelmed by rapidly expanding pro-inflammatory cells. In mouse models of multiple sclerosis, interferon-β (IFN-β) attenuates migration, chemokine secretion and phagocytosis of brain microglia [4]. Our analyses of retinoschisindeficient (Rs1h-/Y) mice revealed type 1 interferon receptor (IFNAR) signaling, indicating that IFN-β-dependent anti-inflammatory mechanisms also occur in retinal microglia. This project therefore aims at elucidating the potential regulatory role of IFN-β on retinal microglia homeostasis. The first part of the project will analyze whether IFNARdeficiency leads to enhanced retinal dystrophy in a mouse model of X-linked juvenile retinoschisis (Rs1h-/Y). Further experiments will study the exact mechanisms of IFN-β signaling in isolated microglia with a special emphasis on the novel interferon-regulated gene AMWAP (activated microglia whey acidic protein) [5].