Development of cell-based therapies for the treatment of retinopathies
Previous and Current Research
Within the last decade the field of retinal research, in particular the development of therapeutic strategies to treat visual impairment and blindness, made significant improvements. The relative easy accessibility of the retina and the increasing knowledge about its architecture and function has made the retina to one of the best studied parts of the CNS, which consequently also entailed major developments towards therapeutic interventions, such as retinal prosthesis, pharmacological, gene therapeutic or cell-based strategies. These approaches provided first evidence that visual function can in principle be restored in retinal degenerative diseases caused by photoreceptor or retinal pigment epithelium (RPE) loss. Conceptually, replacement of photoreceptors/RPE via cell transplantation represents a highly attractive treatment option, as restoration of the native light-processing pathways might most closely resemble normal visual perception. Although diverse cell populations have been used for transplantation experiments into the retina for more than two decades, in depth analysis of the specific molecular requirements of donor cells as well as the host tissue for functional repair have just recently been initiated. Within our lab the requirements for successful photoreceptor or RPE replacement are studied in mouse models of retinal degeneration with the aim to treat visual impairment and blindness.
Future Projects and Goals
For the development of cell-based therapeutic treatments of retinopathies work will be focused on the following key elements:
- Isolation and enrichment of rod/cone photoreceptors and RPE from pluripotent stem cell-derived retinal organoids
- Manipulation of host tissue to enhance cell integration
- Transplantation of photoreceptors/RPE into mouse models of retinopathies
- Analysis of integrated donor cells: morphology, expression patterns, synaptic connections, functionality
Methodological and Technical Expertise
- Cell culture
- Retinal transplantation
- Retinal degeneration models
Santos-Ferreira T, Postel K, Stutzki H, Kurth T, Zeck G, Ader M
Daylight vision repair by cell transplantation.
Stem Cells. 33(1):79–90 (2015)
Carido M, Zhu Y, Postel K, Benkner B, Cimalla P, Karl MO, Kurth T, Paquet-Durand F, Koch E, Münch T, Tanaka EM, Ader M
Characterization of a mouse model with complete RPE loss and its use for RPE cell transplantation.
IOVS. 55(8):5431–5444 (2014)
Ader M, Tanaka EM
Modeling human development in 3D culture.
Curr Opin Cell Biol. 31C:23–28 (2014)
Eberle D, Kurth T, Santos-Ferreira T, Corbeil D, Ader M
Outer segment formation of transplanted photoreceptor precursor cells.
PLoS One. 7(9): e46305 (2012)
Eberle D, Schubert S, Postel K, Corbeil D, Ader M
Increased integration of transplanted CD73-positive photoreceptor precursors into adult mouse retina.
IOVS. 52(9):6462–71 (2011)