Project: X05
Integrated Transcriptomic Profiling of UVB-Induced DNA Damage, Inflammation, and Neovascularisation across Ocular Cell Populations
This crosslinking project investigates how ultraviolet B (UVB) radiation shapes transcriptional stress responses across ocular surface, retinal, and immune cell populations. UVB radiation represents a major environmental genotoxic stressor that contributes to inflammation, tissue remodelling, neovascularization, and degenerative ocular disease. In corneal and limbal tissues, UVB exposure induces direct DNA damage and activates DNA damage response pathways that regulate DNA repair, inflammatory signaling, cell fate decisions, and angiogenic processes. Beyond the cornea, UV-associated pathology has also been implicated in retinal injury, endothelial degeneration, and ocular malignancies, including conjunctival melanoma.
Previous studies within SFB 1607 demonstrated that UV-induced stress in the corneal stem cell niche promotes inflammatory signaling, stromal remodelling, and pathological vascularization associated with diseases such as pterygium. However, most current studies analyze UVB-induced transcriptional responses only in isolated cell populations. This project therefore aims to establish a comprehensive systems-level transcriptomic analysis across multiple ocular and immune cell types to identify conserved UVB response programs and distinguish them from cell type- or disease-specific alterations.
To achieve this, the project integrates a broad panel of primary human ocular cells, immune cells, and disease-associated cell models, including limbal epithelial and stromal cells, pterygium-derived cells, corneal endothelial cells from healthy donors and Fuchs endothelial dystrophy patients, conjunctival melanoma cell lines, retinal pigment epithelial cells, and immune cell populations. Cells will be exposed to standardized UVB irradiation and analyzed at early and late time points to characterize DNA damage signaling, inflammatory activation, repair mechanisms, and angiogenic transcriptional programs.
Bulk RNA sequencing and comparative bioinformatic analyses will identify conserved and cell type-specific transcriptional pathways associated with UVB-induced inflammation, angiogenesis, fibrosis, and degeneration. By integrating expertise across ocular surface biology, retinal disease, immunology, and bioinformatics, this project establishes a novel interdisciplinary framework within SFB 1607 for understanding UV-associated ocular pathology.
The resulting transcriptomic atlas is expected to uncover molecular links between DNA damage, inflammation, and pathological neovascularization, improve the biological validity of in vitro UVB models, and identify potential biomarkers and therapeutic targets for UV-induced ocular diseases, including pterygium, Fuchs endothelial dystrophy, retinal degeneration, and ocular malignancies.
Key Methods
- Standardized UVB irradiation models
- Primary human corneal, limbal, retinal, and immune cell cultures
- Conjunctival and uveal melanoma cell line models
- Bulk RNA sequencing (RNA-seq)
