Bock, Felix - assoc. RG 04

Our research fields are the immunological microenvironment at the corneal graft area as well as the effect of immune modulatory molecules in corneal graft survival. Immune-mediated graft rejections remain the most common cause for graft failure after organ and tissue transplantation. The gold standard to inhibit the immune reaction driven corneal graft failure is the use of corticosteroids. However, this often does not work and using this immunosuppressive agent topically or systemically leads to severe side.

Therefore, there is a great, unmet need to develop more precise therapies to promote corneal graft survival avoiding side effects and increasing the therapeutic efficacy. Understanding the underlying immunological processes at the graft-host microenvironment will help to develop such new strategies.

Reasons for corneal inflammation are manifold. We analyse different inflammatory, clinically relevant pre-conditions of the cornea regarding their cytokine profile as well as their immune cell populations and their effect on corneal graft survival. These findings will help to better understand inflammatory conditions in the cornea which also occur outside the eye like trauma, corrosion or burns and their effect on transplant immunology.

Translationally, we hope to find individualized, clinically available approaches for different underlying diseases to significantly improve high risk corneal transplant survival. The microenvironment plays an important role in several immunological processes.

We could show that pre-incubation of donor tissue with the immune modulator soluble CD83 (sCD83) significantly improves graft survival using a high-risk corneal transplantation model. The induction of tolerogenic mechanisms in graft re- cipients was achieved by a significant upregulation of Tgfb, Foxp3, Il27, and Il10 in the transplant and an increase of regulatory dendritic cells (DCs), macrophages (Mφ), and T cells (Tregs) in eye-draining lymph nodes.

This new therapeutic concept of local graft-tolerance induction could be the seeding point for new therapeutic approaches for other tissue- and solid organ transplantations like skin- or kidney transplantations.

Long term our aim is to establish an interdisciplinary exchange about the induction and the mechanisms of local immune tolerance between corneal transplant immunology, immune competent tissue/solid organ transplant immunology and autoimmune diseases like Sjögrens Syndrom, dry eye disease or rheumatoid arthritis where self-tolerance gets lost and impairs vision.