Project: C06

Translocator protein (TSPO)-induced ROS production by NADPH oxidases in neovascular age-related macular degeneration

Age-related macular degeneration (AMD) is a heterogeneous and progressive chronic disease of the central retina and a leading cause of vision loss among the elderly in the western world. While the etiology of AMD is still not well understood, we and others have shown that local microglia are key players. Targeting of translocator protein (TSPO), a biomarker of brain microgliosis, improved disease outcome in various preclinical model systems of inflammatory diseases. The precise molecular mechanisms underlying these processes, however, remain to be elucidated.

The overall goal of this project is to increase our understanding of how the TSPO/Nox/ROS axis drives retinal inflammatory diseases, such as AMD. To address this, the student will utilise methods including transgenic animal models, FACS, RNA sequencing, proteomics/phosphoproteomics, Immunohistochemistry.

Model of TSPO-mediated ROS production in retinal phagocytes. a In the healthy retina, resident microglia populate the plexiform layers. With their long protrusions, they constantly scan their environment and phagocytose cell debris. Different insults in the RPE and photoreceptor layer rapidly alert microglia. Resident microglia transform into ameboid phagocytes, migrate to the lesion sites and recruit macrophages from the periphery. b In response to these pathological signals, microglia increase pro-inflammatory and pro-angiogenic cytokine expression to resolve neuroinflammation and promote tissue recovery. Adapted from Wolf et al. 2020.

Project leader

Dr. rer.-nat. Anne Wolf

PhD Student

Atena Poor Sasan

Project-related Publications

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