Ueffing Lab

Molecular Biology of Retinal Degenerations

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Innovative techniques for research and diagnostics

To advance the development of new diagnostic approaches and the identification of disease mechanisms in ophthalmology, we have established a special bioanalytical lab with state-of-the-art mass mass spectrometry equipment, expertise in proteomics, metabolomics, bioinformatics, and systems medicine. By deeply analysing retinal protein signatures, pathways and networks, we aim to uncover molecular mechanisms of disease in retinal cells and tissue. This is complemented by cutting-edge imaging techniques, among them super-resolution STED- and Electron-Microscopy to visualize cellular structures in the retina. AI-based tools are developed to detect and analyse disease associated changes in the retina.  We participate in the German National Cohort study (NAKO), coordinating the Competence Unit Retina, and also habour the Helmut Ecker Eye Tissue Resource (HEETR), enabling us to validate molecular findings in patient samples and tissue.

Current Projects:

Mathematical model of protein dynamics and transport in the photoreceptor

The transport of proteins during light and dark adaptation in photoreceptors has been described for only a few proteins, such as transducin, arrestin and recoverin. In retinal photoreceptors, light exposure results in the massive translocation of these proteins between inner and outer segment. We pursue a detailed quantitative analysis of light/dark-regulated protein dynamics in rod outer segments. This enables us to make predictions on the effects of pathological changes that affect photoreceptor function and study the consequences of mutations in a systemic context.  

The German National Cohort (NAKO): Competence Unit Retina

Within the German National Cohort study (www.nako.de) we have developed a tool set for the automated analysis of retinal fundus pictures, including tools to analyse the retinal vasculature, the detection of vessel tortuosity and the analysis of exudates and drusen. These tools allow us to analyse large ophthalmic data sets and to link such data to other medical fields. As the eye can serve as a window to the brain, vasculature, and cell metabolism, we aim to investigate whether early detection of retinal anomalies can help to predict the risk for other systemic diseases such as diabetes, stroke, neurodegenerative, and cardiovascular diseases.

Dynamic adaptive microscopy for label-free multi-parametric imaging in biology and medicine (EU)

Optical microscopy constitutes one of the most fundamental paradigms in biological and medical imaging.

The EU-funded research consortium DynAMic (http://www.dynamic-fet.eu) develops new modalities for ophthalmic imaging, attempting to overcome current limitations, most importantly the constrained depth that currently limits in vivo microscopy and the limited parallel detection of molecular signatures in living tissues. DynAMic develops wavefront-shaping adaptive optics to improve the performance of optical systems, while inversion light diffusion techniques will help it reach 10 times deeper into tissue. In addition, advanced image formation techniques will radically improve label-free high-contrast imaging disrupting the modus operandi of current retinal and neuronal imaging without disturbing the modus agendi of the end users.

Technology to investigate Retinal Degenerations

High end mass spectrometry equipment, 25 years of expertise in proteomic and metabolomic analytics as well as systems medicine strategies to analyse and integrate multimodal data qualities enable tailored solutions and tailored experimental design. We specifically use interactomics to define protein interaction networks and bioinformatics to perform complex analyses of large multi-omics datasets. These techniques allow us to identify functional protein networks and pinpoint relevant signalling pathways as well drivers of disease mechanisms. From there, several targets to intervene into disease are currently tested for future treatment of retinal degeneration.

Helmut Ecker Eye Tissue Resource (HEETR)

The Helmut Ecker Eye Tissue Resource (HEETR) is one of Europe’s largest human eye tissue collections containing eye tissues from >1,200 donors. Founded in 2015 in Manchester by Prof. Paul Bishop, the eye tissue has been transferred to the University Hospital Tübingen under the custodianship of Prof. Simon Clark in December 2020. The biobank contains human eye tissue from post-mortem eyes donated with consent for corneal transplantation and subsequent research use, including macula and peripheral biopsies stored in cryo-preservative. Each donor eye was phenotyped for retinal dystrophies and also genotyped for risk haplotypes associated with the common blinding disease, age-related macular degeneration (AMD). This resource has already contributed to major studies in AMD and other ocular diseases by supplying consented, anonymous, highly characterised human eye tissues to research groups around the world.