Our Research
Vision impairment and blindness caused by the degeneration of the light sensitive photoreceptors and/or the supporting retinal pigment epithelium (RPE), as in age-related macular degeneration (AMD) or retinitis pigmentosa, represents one of the prime causes for disability in industrialized countries, with no effective treatments currently established. Our experimental work focuses on the development of cell-based strategies to replace lost cells in the retina by the transplantation of photoreceptors and RPE cells.
An in vitro expandable cell source for the generation of transplantable photoreceptors and RPE cells will be mandatory for a translation towards clinical application. Therefore, photoreceptor-containing retinal organoids and RPE derived from induced pluripotent stem cells are currently used for transplantation studies in pre-clinical retinal degeneration models to access their potential for functional repair.
Interestingly, we could show that donor mouse photoreceptors actually do not structurally integrate into host retinal tissue, but instead reside at the place of transplantation between the photoreceptor layer and the RPE, the so called sub-retinal space, and exchange cytoplasmic material with host photoreceptors implying a re-interpretation of previous transplantation studies using mouse photoreceptors. Additionally, in recent work we provide evidence that cytoplasmic material transfer is also occuring between cone and rod photoreceptors in the normal mammalian retina, potentially via cytoplasmic tubes formed between involved cells.
In contrast to transplanted mouse photoreceptors, we recently demonstrated structural integration of retinal organoid-derived human photoreceptors into a mouse model of cone degeneration. Incorporated human photoreceptors formed inner and outer segments and appear to synapse to host bipolar cells allowing repair of photopic perception signaled to retinal ganglion cells. Importantly, interaction with host Müller glia and second order neurons emerge to be essential for proper donor photoreceptor maturation and function. Identifying the cellular and molecular mechanism(s) that allow structural and functional donor photoreceptor integration represents a highly important task for the development of cell replacement therapies towards clinical application. Therefore, our lab is currently studying the underlying prerequisites of donor cells as wells as the host environment to define optimized conditions for functional photoreceptor and RPE replacement in the degenerative mammalian retina.