Center for Molecular Medicine Cologne

Felix Bock - assoc. RG 04

Local Immune Modulation in Experimental Ophthalmology

Abstract

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. Vascular endothelial growth factor‐A (VEGF‐A) not only regulates angiogenesis, but is known as a modulator of the immune microenvironment. 

We could show that locally restricted VEGF depletion increases transplantation success by modulating the receiving corneal microenvironment and inducing tolerogenic mechanisms.

The membrane-bound glycoprotein CD83 (mCD83) is a well known surface marker for mature DCs, in humans and mice.

We could show that local application of soluble CD83 induces IDO-mediated immune modulation, increases Foxp3+ T cells, and prolongs allogeneic corneal graft survival.

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.

Clinical and Medical Relevance

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.

Project Related Publications

Schönberg, A., Hamdorf, M., Bock, F. Immunomodulatory Strategies Targeting Dendritic Cells to Improve Corneal Graft Survival. J Clin Med. 2020 Apr 28;9(5)

Salabarria, A.C., Koch M, Schönberg A, Zinser E, Hos D, Hamdorf M, Imhof T, Braun G, Cursiefen C, Bock F. Topical VEGF-C/D Inhibition Prevents Lymphatic Vessel Ingrowth into Cornea but Does Not Improve Corneal Graft Survival.J Clin Med. 2020 Apr 28;9(5):1270.

Salabarria, A.C., Braun, G., Heykants, M., Koch, M., Reuten, R., Mahabir, E., Cursiefen, C. & Bock, F. Local VEGF-A blockade modulates the microenvironment of the corneal graft bed. Am J Transplant (2019).

Willrodt AH, Salabarria AC, Schineis P, Ignatova D, Hunter MC, Vranova M, Golding-Ochsenbein AM, Sigmund E, Romagna A, Strassberger V, Fabbi M, Ferrini S, Cursiefen C, Neri D, Guenova E, Bock F*, Halin C*. ALCAM Mediates DC Migration Through Afferent Lymphatics and Promotes Allospecific Immune Reactions. Front Immunol. 10:759 (2019).

Bock, F., Onderka, J., Braun, G., Schneider, A.C., Hos, D., Bi, Y., Bachmann, B.O. & Cursiefen, C. Identification of Novel Endogenous Anti(lymph)angiogenic Factors in the Aqueous Humor. Invest Ophthalmol Vis Sci 57, 6554-6560 (2016).

Bock, F., Matthaei, M., Reinhard, T., Bohringer, D., Christoph, J., Ganslandt, T. & Cursiefen, C. High-dose subconjunctival cyclosporine a implants do not affect corneal neovascularization after high risk keratoplasty. Ophthalmology 121, 1677-1682 (2014).

Bock, F., Rossner, S., Onderka, J., Lechmann, M., Pallotta, M.T., Fallarino, F., Boon, L., Nicolette, C., DeBenedette, M.A., Tcherepanova, I.Y., Grohmann, U., Steinkasserer, A., Cursiefen, C. & Zinser, E. Topical application of soluble CD83 induces IDO-mediated immune modulation, increases Foxp3+ T cells, and prolongs allogeneic corneal graft survival. J Immunol 191, 1965-1975 (2013).

Bock, F., Maruyama, K., Regenfuss, B., Hos, D., Steven, P., Heindl, L.M. & Cursiefen, C. Novel anti(lymph)angiogenic treatment strategies for corneal and ocular surface diseases. Prog Retin Eye Res 34, 89-124 (2013).

 

Dr. Felix Bock CMMC Cologne
Dr. Felix Bock

Clinic of General Ophthalmology / RG location - LFI Building

assoc. CMMC Research Group

+49 221 478 97789

+49 221 478 86465

Clinic of General Ophthalmology / RG location - LFI Building

Kerpener Str. 62

50924 Cologne

CMMC Profile Page

Curriculum Vitae (CV)

Publications on PubMed

Publications - Felix Bock

Link to PubMed

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