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Here you will find

GRAPHICAL ABSTRACTS

.. which highlight the key findings and methodologies of our publications in a visually engaging and easily understandable format.

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C3a mediates endothelial barrier disruption in brain-derived, but not retinal human endothelial cells

Hannah Nora Wolf, Larissa Gümpelein, Juliane Schikora, Diana Pauly

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International Journal of Molecular Sciences, 2024

This study investigates how human brain and retinal endothelial cells respond to complement anaphylatoxins C3a and C5a in the context of Neuromyelitis optica spectrum disorder (NMOSD). The findings reveal that C3a disrupts the brain endothelial barrier, while retinal endothelial cells maintain integrity under similar conditions, suggesting that the brain may be more vulnerable to pathological IgG transport in NMOSD, and highlighting the potential therapeutic importance of regulating C3a and C5a levels.

Inter-tissue differences in oxidative stress susceptibility reveal a less stable endothelial barrier in the brain than in the retina

Hannah Nora Wolf, Larissa Gümpelein, Juliane Schikora, Diana Pauly

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Experimental Neurology, 2024

This study investigates the effects of oxidative stress on brain and retinal endothelial cells, focusing on their barrier integrity and complement protein profiles in the context of Neuromyelitis optica spectrum disorder (NMOSD). The results reveal that brain endothelial cells are more susceptible to oxidative stress at higher concentrations of H2O2 compared to retinal endothelial cells, which could explain tissue-specific vulnerabilities in NMOSD and similar autoimmune diseases.

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Graphical Abstract NMOSD retinal explants Wolf.jpg

NMOSD IgG impact retinal cells in murine retinal explants

Hannah Nora Wolf, Veronika Ehinger, Larissa Gümpelein, Pratiti Banerjee, Tania Kümpfel, Joachim Havla, Diana Pauly

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Current Issues in Molecular Biology, 2023

Neuromyelitis optica spectrum disorders (NMOSD) involve chronic inflammation of the central nervous system, primarily affecting the optic nerves and spinal cord. This study found that NMOSD immunoglobulins cause retinal stress and degeneration in mouse retinal explants, suggesting that retinal damage in NMOSD might occur independently of relapses.

Complement Factor H-Related 3 Enhanced Inflammation and Complement Activation in Human RPE Cells

Nicole Schäfer, Anas Rasras, Delia M Ormenisan, Sabine Amslinger, Volker Enzmann, Herbert Jägle, Diana Pauly
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Frontiers in Immunology, 2021

Our research identifies Complement Factor H-Related 3 (FHR-3) as a key regulator of the complement system in retinal pigment epithelial (RPE) cells, inducing a pro-inflammatory environment and inflammasome activation, potentially contributing to age-related macular degeneration (AMD). Additionally, our monoclonal antibody, RETC-2-ximab, was shown to mitigate FHR-3's effects, presenting a potential therapeutic target for AMD and related diseases.

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Graphical Abstract Complement in healthy and diseases retina Pauly .jpg

Cell-Type-Specific Complement Expression in the Healthy and Diseased Retina

Diana Pauly, Divyansh Agarwal, Nicholas Dana, Nicole Schäfer, Josef Biber, Kirsten A Wunderlich, Yassin Jabri, Tobias Straub, Nancy R Zhang, Avneesh Gautam, Bernhard H F Weber, Stefanie M Hauck, Mijn Kim, Christine A Curcio, Dwight Stambolian, Mingyao Li, Antje Grosche

Cell reports, 2019

Our single-cell RNA sequencing study of ~92000 mouse retinal cells revealed cell-type-specific complement expression across 11 retinal cell types, with Müller cells and retinal pigment epithelium playing key roles. Aging and transient retinal ischemia significantly alter complement expression, indicating a well-regulated local complement system in the retina.

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