Mechanisms of Müller glia-tumor cell communication in the therapy resistance of retinoblastoma

• Applicant: Professor Dr. Kornelius Kerl
• Subject Area: Ophthalmology ; Hematology, Oncology ; Pediatric and Adolescent Medicine ; Molecular and Cellular Neurology and Neuropathology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 575807044

In this project mechanisms of communication between retinoblastoma tumor cells and Müller glia cells will be explored, with the aim to establish novel target directed therapeutic approaches. Retinoblastoma (RB) are the most common maligne eye tumors of children. Eventhough the prognosis of these children is good, long-term side caused by the current treatment regimens are severe (e. g. by the enucleation of one eye). In preliminary work of this project the applicant demonstrated that RB tumor cells show an intratumoral, cellular heterogeneity with two distinct, predominant subpopulations: i. undifferentiated rod-like tumor cells and ii. more differentiated cone-like tumor cells. Using single-cell-RNA-sequencing of chemotherapy-naive versus chemotherapy-treated RB-samples, the applicant demonstrated that rod-like tumor cells predominantly survive chemotherapy and are therefore considered as chemotherapy resistant. Interestingly, rod-like tumor cells anatomically co-localize with Müller glia cells. In this project we follow the hypothesis that the communication with Müller glia cells results in chemotherapy resistance of rod-like tumor cells. To explore this hypothesis, in this project we will conduct the following experiments: i.) By using spatial RNA-profiles (Xenium technology) of chemo-naive and chemo-pretreated human retinoblastoma, we will evaluate which influence Müller glia cells have on RB tumor cells. ii.) The interaction of Müller glia cells with RB tumor cells will be explored in innovative RB-retina-organoids. These organoids, established in preliminary work, contain Müller glia and RB tumor cells at the same time and are well suited profiling to detect the influence of Müller glia cells on RB tumor cells by using immunohistochemistry, single cell RNA sequencing and spatial RNA profiling. The midterm goal of this project is to prevent the occurence of chemotherapy resistance in RB patients by blocking the communication of Müller glia and RB tumor cells.

• DFG Programme: Research Grants