Principal Investigator, CECAD Cologne
Prof. Dr. Philipp Steven’s group investigates the pathomechanism of dry eye disease and ocular allergy. Their goal is to understand the relationship between these inflammatory diseases and aging-associated changes in the immune regulation of the eye’s conjunctiva-associated lymphoid tissue (CALT) in order to be able to exploit this therapeutically.
Our research: The focus of research is the eye’s conjunctiva-associated lymphoid tissue (CALT), a key structure in the pathogenesis of dry eye disease. The group investigates the role of the body’s own immune regulation of T cells, dendritic cells and macrophages in the development of this disease and how these immune mechanisms may be put to therapeutic use. Therapeutic approaches using immunosuppressants are already being tested in clinical trials.
Our successes: The scientists were the first to systematically describe the lymphoid tissue CALT in a mouse model. Establishing dye-free two-photon microscopy for intravital imaging of the eye and non invasive optical coherence tomography for quantification of mucosal inflammatory processes were other important achievements. Recently using a novel compound for topical anti-inflammatory therapy the group was able to demonstrate the influence of aging on the efficacy of topical cyclosporine for treatment of dry-eye disease. Based on these finding the compound has successfully been tested in a phase II trial.
Our goals: Ultimately Prof. Dr. Steven and his group plan to establish one of the leading research sites for dry eye disease and ocular allergy. The animal models established at the Eye Hospital are internationally competitive. The next goals are to further investigate the role of inflammation and aging-associated pathomechanisms in ocular graft-versus-host disease and the ongoing development of anti-inflammatory treatment strategies.
Our methods/techniques: The group works with cell and organ cultures and complex intravital imaging methods. Molecular biology and flow-cytometric methods are established. Mouse models are used to investigate specific research questions. Successful approaches are transferred to clinical testing.
Figure 1: Conjunctiva-associated lymphoid tissue (CALT) a: histological section of the lymphoid follicle, b: intravital two-photonmicroscopy based on tissue autofluorescence of the corresponding region. Individual cells are visible without the use of artificial dyes.
Figure 2: Clinical phenotype of dry-eye disease: a+b female patient with dry-eye due to Sjögren Syndrome. a: The eye appears almost normal in white light illumination. b: using fluorescent dye staining of the cornea and an irregular tearfilm is visible, causing pain and visual distortion. c: a mouse model of dry-eye shows a similar phenotype with staining of the ocular surface.
Figure 3: Immunohistochemistry of Antigen-presenting cells within Conjunctiva-associated lymphoid tissue (CALT). CALT is thought to play a role in regulating ocular surface immune responses in diseases such as dry-eye, thus serving as a target tissue for novel therapeutic strategies.