Project: B01

Thrombospondin-1 and NF-κB signaling in ocular graft-versus-host disease (GVHD)

Chronic ocular graft-versus-host disease (oGVHD) develops in up to 60% of patients following allogeneic hematopoietic stem cell transplantation. Diagnosis and therapy are challenging due to limited GVHD-specific diagnostic biomarkers especially in early stages and the lack of targeted therapeutic options.

Recent studies from our groups have demonstrated that transient (lymph)angiogenesis takes place in early phases of experimental oGVHD. We demonstrated for the first time that VEGF-C is upregulated in cornea and conjunctiva, and lymphatics grow into the normally avascular cornea. Proof-of-concept experiments demonstrated that desiccating stress during transplantation leads to exacerbation of GVHD including earlier lymphangiogenesis and activation of the IKK/ NF-κB signaling pathway, which is a known regulator of VEGF expression. We furthermore developed advanced deep learning-based algorithms for the analysis of immune cells, nerves, meibomian glands and conjunctival blood vessels in patients, all parameters that are relevant as optical biomarkers for the diagnosis and detection of disease activity and progression in oGVHD.

The project aims to identify new targets related to (lymph)angiogenesis and inflammation that could open the perspective for better and earlier diagnosis as well as specific and preventive treatment of ocular GVHD.

Key methods: in vivo GVHD model, OCT angiography, in-vivo corneal confocal microscopy, RNA isolation, qRT-PCR, bone marrow transplantation, RNAseq, AI-based image analysis