SFB 1607:  Towards immunomodulatory and anti(lymph)angiogenic therapies for age-related blinding eye diseases

• Subject Area: Medicine
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 501530074

Healthy eyes are a prerequisite for good vision. Ophthalmology is the medical discipline responsible for preserving and restoring eye function, which is generally done very successfully. There are, however, eye diseases with poorly understood causes and insufficient therapies. As most of these under-addressable eye diseases are age-associated, the prevalence will increase due to our aging society. Beyond significant loss in quality of life of individuals, leaving these diseases under-investigated will affect and burden society, increasing the need for a specialized research center.Our ongoing DFG research unit 2240 investigated a variety of age-associated eye diseases. We consistently observed two pathomechanisms: faulty cellular immune responses/inflammation and pathologic growth of blood and lymphatic vessels ([lymph]angiogenesis). This supports our overall hypothesis that aberrant cellular immunologic pathology/inflammation and/or pathologic regulation of (lymph)angiogenesis drive clinical manifestations of a variety of age-associated eye diseases. This includes common diseases such as age-related maculopathy, dry eye disease and glaucoma, but also corneal dystrophies, herpetic keratitis, ocular Graft-versus-host-disease and ocular melanoma affecting a large portion of our population (>50% of the 60-years and older). The development of new immune- and (lymph)angiogenesis-modulating therapies is needed. Our CRC has a unique position since there is currently no other international center that focusses on the role of lymphatic/blood vessels and immune cells as the cause of, and new therapeutic target in, age-associated ocular diseases. We therefore propose a new CRC 1607 gathered around the perspective that within 12 years a significant progress in disease understanding and translation into clinical care can be achieved with the following objectives: • Unravel the disease mechanisms of age-associated eye diseases with a special focus on the role of aberrant cellular immunity/inflammation and (lymph)angiogenesis, • To develop innovative new treatment concepts based thereon and, • To transfer at least 25% of projects to early pilot patient data in the last funding period. Tremendous progress has been made in (lymph)angiogenesis and cellular immunity research in recent years. Now it is time for a cross-over into ocular diseases. We included non-ophthalmic experts of (lymph)angiogenesis and inflammation research as well as image analysis and artificial intelligence into our CRC, thereby enabling (i) transfer of external expertise to ophthalmological diseases and (ii) a better use of the eye as an easily accessible model system to unravel disease mechanisms relevant beyond ophthalmology. This will help us to reach our overarching goal: The development of new therapeutic concepts in this area of high unmet need to alleviate to individual and societal burden of age-associated vision loss.

• DFG Programme: Collaborative Research Centres

Current projects

• A01 - Site-specific chronic inflammation and fibrosis in Fuchs endothelial corneal dystrophy (Project Heads Matthaei, Mario Magnus Goswin ;  Odenthal, Margarete )
• A02 - Strain- and metabolism-dependent genetic variations of (lymph)angiogenesis: identification of candidates and influence on corneal wound healing (Project Heads Clahsen, Thomas ;  Reis, André )
• A03 - Personalized anti(lymph)angiogenic therapy and immunomodulation in high-risk corneal transplantation (Project Heads Bock, Felix ;  Cursiefen, Claus )
• A04 - Metabolic control of corneal hem- and (lymph)angiogenesis (Project Heads Hadrian, Karina ;  Kashkar, Hamid )
• A05 - The role of limbal stem cells in corneal (lymph)angiogenesis, inflammation and UV-induced pterygium pathogenesis (Project Heads Notara, Ph.D., Maria ;  Schumacher, Björn )
• B01 - Thrombospondin-1 and NF-κB signaling in ocular graft-versus-host disease (GVHD) (Project Heads Pasparakis, Manolis ;  Steven, Philipp )
• B02 - Role of macrophage-dependent osmoprotective and hypoxic signal transduction in inflammatory corneal diseases (Project Heads Hos, Deniz ;  Jantsch, Jonathan )
• B03 - CD83-based immunomodulation in ocular surface inflammation such as dry eye (Project Heads Howaldt, Antonia ;  Steinkasserer, Alexander )
• B04 - Variability and organ specificity of lymphatic vessel–dendritic cell interactions in the eye (allergic conjunctivitis) (Project Heads Kiefer, Friedemann ;  Schlereth, Simona )
• C01 - Mitochondrial DNA at the interface between mitochondrial dysfunction and neuroinflammation in glaucoma (Project Heads Liu, Hanhan ;  Trifunovic, Aleksandra )
• C02 - The lymphatic regulator SVEP1 in Schlemm‘s canal function– a therapeutic target for glaucoma (Project Heads Prokosch, Verena ;  Schulte-Merker, Stefan )
• C03 - In depth investigation of the molecular signaling mechanisms and cellular function of midkine, neuropilin-2 and sFLT1 in conjunctival and uveal melanoma (Project Heads Bosch, Jacobus J. ;  Heindl, Ludwig M. )
• C04 - Tumor-microenvironmental alterations during pathogenesis and therapy of conjunctival melanoma (Project Heads Schlereth, Simona ;  Wunderlich, Frank Thomas )
• C05 - Galectins in the pathogenesis of retinal neovascular and inflammatory diseases (Project Heads Langmann, Thomas ;  Rüger, Maria Adele )
• C06 - Translocator protein (TSPO)-induced ROS production by NADPH oxidases in neovascular age-related macular degeneration (Project Head Wolf, Anne )
• C07 - NLRP3 inflammasome as a therapeutic target in atrophic age-related macular degeneration (Project Head Krohne, Tim Ulrich )
• Z01 - Therapeutic Protein Production Facility (Project Head Koch, Manuel )
• Z02 - Imaging Core Unit (ICU) (Project Head Bock, Felix )
• Z03 - Administration (Project Head Cursiefen, Claus )
• Z04 - Integrated Research Training Group “Eye and Inflammation” (EI) (Project Heads Bock, Felix ;  Prokosch, Verena )
• Z05 - Data management, data mining and image analysis (Project Heads Beyan, Oya ;  Bozek, Katarzyna )

• Applicant Institution: Universität zu Köln
• Participating Institution: Max-Planck-Institut für Stoffwechselforschung
• Participating University: Friedrich-Alexander-Universität Erlangen-Nürnberg; Universität Münster
• Spokesperson: Professor Dr. Claus Cursiefen