TU Dresden


CLEANSIGHT: An RPE-based screening platform

The project based group "CLEANSIGHT" started in January 2017, after receiving 1,56 million EUR in funding from the BMBF under the VIP+ program. The purpose of this project is to validate a retinal pigment epithelium (RPE)-based screening platform that reveals classes of small molecules, which have the potential to be further developed into therapeutic drugs, to cure macular and retinal degenerative diseases. Such diseases include retinitis pigmentosa, which is a rare hereditary disorder leading to early onset blindness, and age-related macular degeneration (AMD), which is the leading cause for blindness in the industrial world. The project idea was initiated in a collaborative effort between Prof. Dr. Elly Tanaka, Prof. Dr. Marius Ader and Dr. Mike Karl based on a patented protocol by Prof. Tanaka that allows the efficient generation of RPE from human pluripotent stem cells (1-3). In 2013, Dr. Seba Almedawar (CLEANSIGHT project leader) joined the group of Prof. Tanaka to realize the project´s idea. Together with the rest of the team they upscaled RPE production, and developed the screening platform, taking the human RPE protocol to the next level, and providing the means for the BMBF VIP+ funding for the CLEANSIGHT project.

Figure: Human pluripotent stem cell (hPSC)-derived RPE cells, upscaled and grown in a 96 high-throughput cell culture plate, form a homogeneous pigmented cell monolayer. In the right corner is a bright field confocal microscope picture showing characteristic hexagonal shape and pigmentation of these RPE cells.


RPE (retinal pigment epithelium) related retinal degenerative diseases can be inherited, such as retinitis pigmentosa (RP), or age-dependent, such as age-related macular degeneration (AMD). In both cases, patients suffer from severe vision loss and ultimately blindness. Currently, there are no effective therapies to prevent and restore vision loss due to retinal degeneration. The RPE represents a prime target to develop therapeutic drugs for a broad spectrum of patients.

One of the most important RPE cell functions - the phagocytosis of daily shed photoreceptor outer segments (POS) - is essential for photoreceptor viability and visual function. Importantly, defects in RPE phagocytosis, either due to gene mutations in RP or due to still not fully understood processes in AMD patients, lead to accumulation of POS debris at the interface of photoreceptors and RPE (in the so-called subretinal space), which is sufficient to cause and contribute to retinal degeneration and vision loss, respectively. Thus, CLEANSIGHT pursues the identification of therapeutic targets to control RPE phagocytosis. Until now, there are no effective treatments established for such diseases, in part due to lack of experimental model systems. Stem cell based technologies, like CLEANSIGHT's human RPE screening platform, offer the chance to develop disease models and high-throughput assays for identification of compounds with therapeutic potential.

Collaboration projects

The ability to produce virtually unlimited amounts of high quality human RPE helped the researchers establish other collaboration projects, which also serve the aims of CLEANSIGHT project. Such collaborations include the enrichment of RPE for transplantation (Miltenyi collaboration, BMBF ReSight project, Prof. Marius Ader), and bringing the platform to an industry level, where bigger libraries can be screened (collaboration with Evotec).

Future projects and goals

The aims of our ongoing and future research are

  • Identify classes of drug-like chemical compounds with therapeutic potential for human RPE.
  • In vivo validation and development of hits obtained in the primary screen.
  • Expanding the platform to other retinal degenerative disease, such as Best1 associated retinal dystrophy (in collaboration with Prof. Olaf Strauss; Charite, Berlin).

Selected publications

Zhu Y, Carido M, Meinhardt A, Kurth T, Karl MO, Ader M, et al. Three-Dimensional Neuroepithelial Culture from Human Embryonic Stem Cells and Its Use for Quantitative Conversion to Retinal Pigment Epithelium. PLoS One. 2013; 8(1).

Zhu Y, Schreiter S, Tanaka EM. Accelerated Three-Dimensional Neuroepithelium Formation from Human Embryonic Stem Cells and Its Use for Quantitative Differentiation to Human Retinal Pigment Epithelium. Methods Mol Biol. 2014; 1307:345-55.

Carido M, Zhu Y, Postel K, Benkner B, Cimalla P, Karl MO, et al. Characterization of a Mouse Model With Complete RPE Loss and Its Use for RPE Cell Transplantation. Invest Ophthamol Vis Sci. 2014; 5431-44.

Project leader

Seba Almedawar

Dr. Seba Almedawar
+49 (0)351 458 82136


The CLEANSIGHT group core members are from left to right:

Dr. Sven Schreiter, postdoctoral fellow, in vitro validation

Susann Krause, Technician

Dr. Seba Almedawar, postdoctoral fellow, project leader

M.Sc. Josefin Kühne, Technician

Dr. Dominic Eberle, postdoctoral fellow, in vivo validation

CLEANSIGHT team also includes:

Susanne Luft, Technician

Dr. Mike O. Karl, PI

Prof. Dr. Marius Ader, PI

Prof. Dr. Elly Tanaka, PI (previous CRTD director)