DFG priority programme funds innovative eye research in Dresden

Within the Priority Programme 2127 “Gene and Cell-based Therapies to Counteract Neuroretinal Degeneration” the German Research Foundation (DFG) provides funding of more than one million Euros for three years to four research groups at the Center for Regenerative Therapies Dresden (CRTD) and the Biotechnology Center (BIOTEC), both part of the Center for Molecular and Cellular Bioengineering (CMCB) of the TU Dresden, as well as at the German Center for Neurodegenerative Diseases (DZNE) in Dresden.

The SPP2127 brings together 29 experts in vision research and clinical ophthalmology to develop gene- and cell-based therapies for the treatment of currently incurable blinding diseases in a German-wide network. The funded projects will further strengthen this research direction within the Dresden life science network including pioneering approaches in regenerative therapies utilizing human induced pluripotent stem cells (hiPSC), genome engineering and label-free sorting technologies.

Since important anatomical features of the human retina, such as the macula, are not present in typical laboratory animals, the lab of Dr. Mike Karl, group leader for Retinal Degeneration and Regeneration at the DZNE and affiliated with the CRTD, has developed 3D retinal organ-like systems, so-called organoids, from hiPSC. He will use these organoids for human disease modelling, especially for macular degeneration. Key for future therapies is to understand the pathological processes during photoreceptor degeneration including tissue–remodelling and scar formation. In addition, these human model retinas represent potential preclinical models to translate and optimize the integration of transplanted photoreceptors into the host tissue for future vision restoration therapies by cell replacement.

Dr. Marius Ader, Professor for Cell Replacement in the Mammalian Retina at the CRTD, an expert in photoreceptor cell transplantation, receives funding for a joint research project with Dr. Jochen Guck, Professor for Cellular Machines at the BIOTEC, to extract sufficient numbers of human photoreceptors from 3D organoids. To this end, the team will purify and sort high quantities of rod and cone photoreceptors based on their morphological and mechanical fingerprints by real-time deformability cytometry (RT-DC), a technique developed in the Guck laboratory. This label-free sorting will provide high-quality and high-quantity photoreceptor material for cell transplantation therapies.

A third funded project aims at establishing precise genomic engineering in retinal photoreceptors as a potential future therapeutic approach by in vivo repair of disease-causing gene mutations. This project is led by Dr. Volker Busskamp, group leader for Neuronal Cell Type and Circuit Engineering at the CRTD, together with his colleague Dr. Knut Stieger, Professor for Experimental Ophthalmology (University of Giessen). Normally, following gene editing, precise DNA repair - cut and paste of a mutation-free gene sequence - only occurs in dividing cells. In post-mitotic cells, such as photoreceptors, genomic engineering normally results in DNA breaks that are randomly tethered resulting in additional unwanted mutations. Therefore, the team will exploit a recently discovered DNA repair mechanism to facilitate precise (cut and paste) repair of genomic mutations in photoreceptors using preclinical models.

Website of Prof. Dr. Marius Ader (CRTD): http://www.crt-dresden.de/research/research-groups/core-groups/crtd-core-groups/cell-replacement-in-the-mammalian-retina/

Website of Dr. Volker Busskamp (CRTD): http://www.crt-dresden.de/research/research-groups/core-groups/crtd-core-groups/neuronal-cell-types-and-circuit-engineering/

Website of Prof. Dr. Jochen Guck (BIOTEC): http://www.biotec.tu-dresden.de/research/guck.html

Website of Dr. Mike O. Karl, MD (DZNE, CRTD): https://www.dzne.de/karl

http://www.crt-dresden.de/research/research-groups/core-groups/crtd-core-groups/retinal-development-and-regeneration/

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