About

Focus Area “A” – Inflammatory and (lymph)angiogenic reduction of corneal transparency and vision:
addresses insufficient understanding of and insufficient therapies for inflammatory and (lymph)angiogenic reduction of corneal transparency and vision loss at the cornea. This means that all projects work on the same ocular tissue and are closely connected by several joint mechanisms (corneal) lymphangiogenesis, UV irradiation, dendritic cell [DC] activation etc.). The cornea is the transparent “windscreen” of the eye, which can lose its transparency by several causes:

The first project A01, therefore targets the modulation of inflammatory and secondary fibrotic extracellular matrix (ECM) pathology in Fuchs corneal endothelial dystrophy, the most common disease leading to corneal transplantation; A02 addresses strain-dependent genetic variations of (lymph)angiogenesis that can be identified using the cornea as a model system in Collaborative Cross Line Mice, thereby identifies novel endogenous regulators of lymphangiogenesis in metabolically altered mice and examines their functional influence on corneal wound healing. A02 in addition will identify and functionally characterize additional new endogenous modulators of lymphangiogenesis in collaboration with all other A-projects and several B- and Cprojects. A03 addresses the disease-specific and individual differences in a variety of high- and low-risk corneal transplantation settings (characterized by pathologic [lymph]angiogenesis and DC activation) and aims to develop personalised anti-lymphangiogenic and immunomodulatory therapeutic approaches to promote graft survival after corneal transplantation (with a special focus on UV light-mediated alterations of lymphatic vessels and altered DC activation). In addition, A04 examines the novel concept of metabolic control of corneal hem- and (lymph)angiogenesis also with respect to corneal transplant immunology. A05 studies the role of ABCB5+ limbal stem cell populations in corneal (lymph)angiogenesis, inflammation and UV-induced pterygium pathogenesis (again, a disease characterized by aberrant [lymph]angiogenesis).

Focus Area “B” – Severe ocular surface inflammation and (lymph)angiogenisis in dry eye disease, ocular GVHD, and allergy:
studies mechanisms and new therapeutic approaches in severe ocular surface inflammation with a focus on dry eye disease, ocular GVHD and allergy. All projects are connected by the investigation of inflammatory changes at the ocular surface, i.e. corneal surface, conjunctival surface and tear film, and focus on dampening inflammatory and lymphangiogenic activation in that ocular location. Here, in B01 the novel pathogenic role of lymphatic vessels in ocular graft versus host disease is studied. A specific focus is on the role TSP1 and NFKb signaling in lymphangiogenesis and inflammation in oGVHD. In B02 the role of osmosensation in macrophage activation and (lymph)angiogenesis in inflammatory diseases of the ocular surface is analyzed. Project B03 tests the hypothesis that CD83-based immunomodulation can alter immunological diseases of the ocular surface (using various disease models with a special focus on dry eye disease and herpetic keratitis). Finally, the variability and organ-specificity of lymphatic vessel‒DC interactions in the eye – also using the eye as a model – are analyzed (using ocular conjunctival allergy and a new innovative model as an example) in B04.

Focus Area “C” – Immune-mediated and (neo)vascular vision loss in glaucoma, ocular tumours, and AMD:
studies immune-mediated and neovascular vision loss in glaucoma, ocular tumours and age-related maculopathy. These groups are working mainly on tissue in the posterior part of the eye and are—besides the two main pathogenic mechanisms—linked by investigating the effects of altered inflammation and (lymph)angiogenesis primarily on retinal and uveal tissues. Again, it also aims to develop new therapeutic concepts. Here, the role of mitochondrial dysfunction in mediating retinal neuroinflammation in glaucoma is studied in C01, as are the novel roles of lymphangiogenic mediators in Schlemm’s canal and their relevance for glaucoma pathogenesis and therapy in C02, a very timely topic in glaucoma research. SVEP-1 will be characterized as a novel lymphangiogenesis modulator and therapeutic target in glaucoma. C01 and 2 will interact closely. The second two projects deal with (lymph)angiogenesis in ocular tumours with a special focus on midkine in regulating tumour growth and (lymph)angiogenesis (C03), as well as the role of DCs and inflammatory cytokines in the therapeutic targeting of conjunctival melanoma (C04). Furthermore, project area C deals with aberrant cellular immunity in immune-mediated and neovascular vision loss in AMD. Here, one topic is the role of galectins in the retina and its influence on AMD (C05), as well as the role of reactive oxygen species production in retinal inflammatory diseases (C06) and, finally, the role of inflammasome in degenerative retinal diseases such as AMD (C07). C05-07 are closely linked through their work on microglia as inflammatory target cell.

Focus Area “Z” – Core Units: To supplement all project areas and individual projects as well as to strengthen our core goals of TRANSLATION and optimized IMAGING five core units are in project area Z. This includes
Z01: Translational core unit: “Therapeutic antibody production facility” The aim of Z01 is to foster
translation of basic research into the clinic throughout the whole funding period of CRC1607 (PI: Prof. M. Koch).
Z02: “Imaging Core Unit (ICU)” comprises a state-of-the-art and worldwide unique animal eye imaging facility funded by the Medical Faculty of UoC and DFG during the FOR2240 period at our department (2015-2023; PI: Prof. F. Bock).
Z03 is the administrative core unit, also responsible for Clinician-Scientist support (PI Prof. C. Cursiefen).
Z04: The Research Training Group Eye and Inflammation is of essential importance to educate and train young scientists for the field of the eye research and inflammation leading CRC, but also nationwide. PIs: Prof. V. Prokosch and Prof. F. Bock.
Z05 – INF project: This project is about data storage and data mining (mainly driven by the director of the Institute of Medical Informatics, Prof. Oya Beyan) and AI-based image analysis (PI: Prof. K. Bozek).

1. Age-related blinding eye diseases are increasing in prevalence. The pressure to better understand and, based on that understanding, target these diseases with novel concepts is significantly increasing.
2. It is increasingly evident that most of these vision-threatening age-related diseases are associated with aberrant inflammation, (lymph)angiogenesis and cellular immunity.
3. A dramatic knowledge shift recently occurred in the perception of the role of lymphatic vessels in numerous diseases, including the eye, thus making them a novel, interesting therapeutic target also in ophthalmology (with the help of external experts). Same applies to the field of cellular immunity/inflammation.
4. Now it is necessary to broaden our pathomechanistic understanding of the interface between cellular immunity and (lymph)angiogenesis by including more (outside) expertise and focus on the eye and its diseases to move forward to the next level, that is better disease understanding and development of new therapeutic concepts for age-related blinding eye diseases.
5. Our previous DFG Forschungsgruppe (RU 2240; www.for2240.de) has created a very synergistic group of experts in ocular (lymph)angiogenesis and cellular immunity research in Cologne. Young talents have developed within that framework and e.g. the CCSP and this group with now manifold interactions within the MF (Medical Faculty), CMMC, CECAD etc. in Cologne needs longterm structural stability to even further grow and contribute as lighthouse to translational research in Cologne.
6. Pharmaceutical industry recently is increasingly interested in ophthalmology thus increasing the chances for translational progress. Here, we currently see a considerable need for additional clinically oriented basic research and preclinical testing.
7. The diseases mentioned here can partly be classified as “widespread diseases” (“Volkskrankheiten”). Half of all 80-year-olds in Germany suffer from one or other form of AMD, 20% of over 50-year-olds suffer from various forms of glaucoma. More than 5% of over 50-year-olds suffer from corneal dystrophies (such as Fuchs endothelial dystrophy), which subsequently lead to corneal transplantation and possible rejection responses. Dry eye disease also affects about 10% of the total population – just to give some examples. Moreover, these unmet needs also apply to several rare but paradigmatic diseases.
8. We want to promote the eye not only as target for eye disease-oriented research, but also as model system. For example, the unravelling of the molecular mechanisms of melanoma cell and lymphatic vessel interaction in ocular melanoma should provide universal insights that are also valid outside the eye.