Project Details
Projekt
Microglial dynamics in retinal diseases: Müller cells and T cells as local and peripheral interacting partners
Subject Area
Ophthalmology
Experimental Models for the Understanding of Nervous System Diseases
Molecular Biology and Physiology of Neurons and Glial Cells
Experimental Models for the Understanding of Nervous System Diseases
Molecular Biology and Physiology of Neurons and Glial Cells
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 559333543
This project aims to address critical gaps in the understanding of how microglial cells, the resident tissue macrophages of the retina, interact with Müller cells as local cues and T cells as invading interaction partners from the periphery. The focus is on studying these interactions in the context of diabetic retinopathy (DR), a leading cause of vision loss, and during adeno-associated virus (AAV)-vectored gene therapy, which holds great potential for effectively treating patients with DR. Using advanced diabetic models and genetically engineered pigs with high translational potential, the research will specifically address the following goals: (i) Microglia, found in different regions of the retina, behave differently depending on local cues such as metabolic stress or chemokines like CCL2, which are primarily derived from Müller cells. The study will investigate how these factors shape microglial behavior in both central and peripheral parts of the retina. (ii) A major goal is to define how microglia interact with both local retinal cells such as Müller cells and peripheral immune cells such as CD4+ T cells to understand their role in immune regulation and retinal inflammation. (iii) The project will investigate how microglial diversity influences retinal responses to AAV-mediated gene therapy. As AAV-mediated therapies are being developed for retinal diseases including DR, the study will address how they modulate immune responses, particularly in the diabetic retina. (iv) Single-cell proteomics, a cutting-edge method, will be used to study the individual molecular profiles of retinal cells, providing insights into the immune response and how microglia and Müller cells interact. This will contribute to a deeper understanding of the complexity of retinal diseases and refine therapeutic strategies. By combining expertise in immunology and retinal biology, this interdisciplinary project will use advanced techniques and models that closely mimic human conditions. The overarching goal is to expand knowledge of the cues driving microglial responses and heterogeneity to help develop new therapeutic strategies for retinal and CNS diseases.
DFG Programme
Priority Programmes
