Lymph- and hemangiogenesis in ocular graft-versus-host disease

• Applicant: Professor Dr. Philipp Steven, since 6/2022
• Subject Area: Ophthalmology
• Term: from 2018 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 257498687

Ocular graft-versus-host disease (ocular GvHD) is a potentially sight-threatening disease that occurs in 60-80 % of patients following allogeneic hematopoetic stem cell transplantation (aHSCT). Whereas acute ocular GvHD is rare and onsets within the first months after aHSCT, chronic ocular GvHD is frequent and onsets during or after reduction of systemic immunosuppression. The latter leads to severe dry-eye disease with destruction of the cornea, lacrimal gland and Meibomian glands and consecutive conjunctival scarring. In systemic GvHD it has recently been shown experimentally that hem- and lymphangiogenesis play a role in the pathogenesis of disease and anti-angiogenic therapy has been demonstrated to reduce severity of GvHD and mortality. This project will investigate the role of hem- and lymphangiogenesis in acute and chronic GvHD mouse models to test the hypothesis that systemic but also topical anti-angiogenic substances may reduce ocular GvHD. Besides morphometric investigations, molecular analyses, detailed histology and intravital imaging techniques are applied. Furthermore using non-invasive imaging techniques in patients undergoing aHSCT, it is prospectively investigated, whether ocular surface lymphatic and blood vessel morphology correlate with ocular GvHD activity. Overall the project investigates potential disease mechanisms in ocular GvHD that are very likely to play a key role and that have the potential to serve as therapeutic and diagnostic targets hereby filling an actual gap in clinical care of patients with ocular GvHD. In detail this project aims to answer the fundamental question if lymph- and hemangiogenesis is augmented during ocular GvHD, and in the following if a targeted inhibition of lymph- and/or hemangiogenesis reduces or even prevents ocular GvHD.

• DFG Programme: Research Units
• Subproject of: FOR 2240: (Lymph)Angiogenesis And Cellular Immunity In Inflammatory Diseases Of The Eye
• Co-Investigator: Professor Dr. Olaf Penack
• Ehemalige Antragstellerin: Uta Gehlsen, Ph.D., until 5/2022