PUBLICATIONS
Here you will find recent publication of Diana Pauly and her group members about complement system in vision research.
Juliane Schikora, Aaron Dort, Hannah N. Wolf, Mihály Józsi, Richard B. Pouw, Thomas Bertelmann, Dirk Bahlmann, Christian van Oterendorp, Nicolas Feltgen, Hans Hoerauf, Diana Pauly*# and Jannis Klemming*
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2025, Journal of Translational Medicine
*These authors share senior authorship.
# corresponding author
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This pilot study investigated inflammatory mediators and complement components in the aqueous humour of patients with non-exudative age-related macular degeneration (AMD) compared to controls. The results showed decreased levels of complement component C4, interleukin-10 (IL-10), and factor I (FI) in the AMD group, suggesting a potential role for complement dysregulation and altered cytokine profiles in disease progression. A positive correlation was observed between drusen volume and CCL4 levels, indicating that higher drusen burden may be linked to inflammatory activity. Notably, smoking was associated with increased levels of pro-inflammatory proteins (CCL7, IL-7), and sex differences were detected in factor B and C4B. These findings underscore the importance of complement and inflammatory processes in non-exudative AMD and provide the basis for further investigations into targeted therapeutic strategies.
DEVELOPMENT AND CHARACTERIZATION OF NOVEL ELISAS FOR THE SPECIFIC QUANTIFICATION OF THE FACTOR H-RELATED PROTEINS 2, 3, 4 AND 5
Mara van Rossum, Bert R.J. Veuskens, Mieke C. Brouwer, Gerard van Mierlo, Laura Lucientes-Continente, Elena Goicoechea de Jorge, Barbara Uzonyi, Alexandra T. Matola, Mihály Józsi, Günter Müller, Anita Meter-Arkema, Felix Poppelaars, Diana Pauly, Richard B. Pouw* and Erik Toonen*
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in press, Journal of Innate Immunity
*These authors share senior authorship.
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This study tackles the challenge of accurately measuring Factor H-Related (FHR) proteins, key but poorly understood regulators of the complement system’s alternative pathway. By generating new monoclonal mouse antibodies and carefully validating their specificity and sensitivity, the researchers developed four ELISAs capable of quantifying FHR-2, FHR-3, FHR-4, and FHR-5 with no cross-reactivity to other FHRs or Factor H (FH). These assays showed strong recovery rates (81–116%) and consistently low variation (CV <15%), highlighting their robustness. With these tools in hand, large-scale patient screening becomes feasible, setting the stage for deeper insights into the roles of FHR proteins in human health and disease.
Hannah N Wolf, Larissa Guempelein, Juliane Schikora, Diana Pauly
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2024, International Journal or Molecular Science
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This study investigated how two specific complement system molecules, C3a and C5a, affect cells of the blood-brain barrier (HBMEC) and the blood-retina barrier (HREC). These molecules are involved in neuromyelitis optica spectrum disorder (NMOSD), a condition that causes damage in the brain and vision. Particular autoantibodies, AQP4-IgG, are known to attack brain tissue, but its impact on retinal tissue is unclear.
Our findings show that C3a weakens the barrier in blood-brain cells (HBMEC), increasing their permeability and making the tissue more vulnerable to damage. Interestingly, blood-retina cells (HREC) responded differently—they maintained their stability and were not disrupted by C3a. Additionally, C5a was found to play a protective role in brain cells, reducing the harmful effects of C3a.
Overall, the study suggests that retinal cells are more resistant to stress caused by these molecules compared to brain cells. This could mean that the retina is better protected against the harmful transport of AQP4-IgG.
Hannah N Wolf, Larissa Guempelein, Juliane Schikora, Diana Pauly
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2024, Experimental Neurology
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​This study examined the susceptibility of brain and retinal endothelial barriers to oxidative stress, highlighting a greater fragility in brain endothelial cells compared to retinal cells. Using hydrogen peroxide to induce oxidative stress, the researchers observed distinct growth patterns between the two cell types, with brain endothelial cells experiencing a more pronounced barrier breakdown at higher stress levels. Both cell types produced complement factors H and I, but their secretion patterns were altered under oxidative conditions. These results suggest that tissue-specific differences in stress responses may contribute to the pathophysiology of Neuromyelitis Optica Spectrum Disorder (NMOSD) and could inform future therapeutic strategies targeting endothelial barriers in autoimmune diseases affecting the brain and retina.
Josef Biber, Yassin Jabri, Sarah Glänzer, Aaron Dort, Patricia Hoffelner, Christoph Q. Schmidt, Oliver Bludau, Diana Pauly*, Antje Grosche*
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2024, Journal of Neuroinflammation
*These authors share senior authorship.
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​This study investigates the therapeutic potential of adeno-associated viruses (AAVs) engineered to express truncated human complement factor H (FH) variants in treating retinal diseases exacerbated by complement system overactivity. Following ischemic injury in mouse retinas, the AAVs targeted gliotic Müller cells, resulting in decreased complement activation, improved microglia activity, and morphological recovery, indicating the promise of this gene therapy approach for retinal conditions lacking effective treatments.
Hannah N Wolf, Veronika Ehinger, Larissa Guempelein, Tania Kuempfel, Joachim Havla, Diana Pauly
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2023, Current Issues in Molecular Biology
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We have added the most important results and take aways in a short blog entry which you can find here.
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​This exploratory study analyzed the effects of NMOSD immunoglobulins (IgG) on mouse retinal explants, revealing that NMOSD IgG increased gliosis and decreased chemokine release, potentially altering the retinal cellular environment and contributing to retinal degeneration independent of relapse activity. These findings suggest that NMOSD may cause primary retinopathy through mechanisms involving retinal glial cells.
Randy Zauhar, Josef Biber, Yassin Jabri, Mijin Kim, Jian Hu, Lew Kaplan, Anna M. Pfaller, Nicole Schäfer, Volker Enzmann, Ursula Schlötzer-Schrehardt, Tobias Straub, Stefanie M. Hauck, Paul D. Gamlin, Michael B. McFerrin, Jeffrey Messinger, Christianne E. Strang, Christine A. Curcio, Nicholas Dana, Antje Grosche*, Mingyao Li*, Dwight Stambolian* and Diana Pauly*
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2022, Frontiers in Immunology
*These authors share senior authorship.
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​This study highlights the regional differences in cellular expression of complement proteins within the retina and its supporting tissues, noting significant variations between the macular and peripheral areas. These findings suggest that the location within the retina is crucial for understanding the role of complement in retinal diseases.
Schäfer N, Rasras A, Ormenisan D, Amslinger S, Enzmann V, Jägle H, Pauly D.
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2021, Frontiers in Immunology
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​This study reveals that Complement Factor H-Related 3 (FHR-3) binds to oxidative stress epitopes, competes with Factor H, and is internalized by retinal pigment epithelial (RPE) cells, leading to increased expression of complement components and receptors. FHR-3 induces a pro-inflammatory microenvironment via inflammasome activation and cytokine secretion in RPE cells, suggesting its role as a trigger for complement activation in degenerative diseases and a potential therapeutic target.
Poppelaars F, Goicoechea de Jorge E, Jongerius I, Baeumner AJ, Steiner MS, Józsi M, Toonen EJM, Pauly D; SciFiMed consortium.
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2021, Frontiers in Immunology
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​This perspective review highlights the critical role of the human Factor H (FH) protein family in various diseases characterized by complement dysregulation, emphasizing the need to address major challenges such as functional role controversies, quantification discrepancies, and the lack of validated tools and suitable animal models. The authors advocate for a strong multidisciplinary approach, facilitated by collaborations like the SciFiMed Consortium, to comprehensively analyze and understand the FH protein family.
Enzbrenner A, Zulliger R, Biber J, Pousa AMQ, Schäfer N, Stucki C, Giroud N, Berrera M, Kortvely E, Schmucki R, Badi L, Grosche A, Pauly D*, Enzmann V*.
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2021, International Journal of Molecular Science
*These authors share senior authorship.
Jabri Y, Biber J, Diaz-Lezama N, Grosche A, Pauly D.
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2020, International Journal of Molecular Science
Schäfer N, Wolf HN, Enzbrenner A, Schikora J, Reichenthaler M, Enzmann V, Pauly D.
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2020, Antioxidants
Mietzner R, Kade C, Froemel F, Pauly D, Stamer WD, Ohlmann A, Wegener J, Fuchshofer R, Breunig M.
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2020, Pharmaceutics
Pauly D*, Agarwal D*, Dana N, Schäfer N, Biber J, Wunderlich KA, Jabri Y, Straub T, Zhang NR, Gautam AK, Weber BHF, Hauck SM, Kim M, Curcio CA, Stambolian D, Li M, Grosche A.
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2019, Cell Reports
* These authors share first authorship.
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Trakkides TO, Schäfer N, Reichenthaler M, Kühn K, Brandwijk RJMGE, Toonen EJM, Urban F, Wegener J, Enzmann V, Pauly D.
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2019, Antioxidants
von Berg L, Stern D, Pauly D, Mahrhold S, Weisemann J, Jentsch L, Hansbauer EM, Müller C, Avondet MA, Rummel A, Dorner MB, Dorner BG.
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2019, Scientific Reports
Schäfer N, Grosche A, Schmitt SI, Braunger BM, Pauly D.
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2017, Frontiers of Molecular Neuroscience