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Cell Replacement in the Mammalian Retina - Previous and current research

Retinal degeneration due to loss of photoreceptors represents one of the prime causes for vision impairment and blindness in industrialized countries. Our experimental work focuses on the development of cell-based strategies to replace or support cells in the degenerative mammalian retina by using stem cell-derived photoreceptors and retinal pigment epithelium for transplantation.

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.

In recent years we provided proof-of-concept studies for photoreceptor survival and maturation following retinal transplantation into mouse models of retinal degeneration, defined the optimal developmental stage for transplantable photoreceptors, identified cell surface markers for efficient enrichment of rod photoreceptors, and demonstrated daylight vision repair following transplantation of cone-like photoreceptors into a mouse model with degenerated cones.

An in vitro expandable cell source for the generation of transplantable photoreceptors and RPE cells will be mandatory for the translation towards clinical application. Therefore, photoreceptor-containing retina organoids and RPE from pluripotent stem cells (mouse and human embryonic and induced pluripotent stem cells) are currently used for transplantation studies in pre-clinical retinal degeneration models to access their potential for functional repair.

Recent results provide evidence that donor photoreceptors actually do not structurally integrate into host retinal tissue, that still contains endogenous photoreceptors, but instead reside between the photoreceptor layer and the RPE, the so called sub-retinal space, and exchange intracellular material with host photoreceptors. Our results contradict the common view that transplanted photoreceptors migrate and integrate into the photoreceptor layer of recipients and therefore imply a re-interpretation of previous photoreceptor transplantation studies. Actually, the observed interaction of donor with host photoreceptors may represent an unexpected mechanism for the treatment of blinding diseases in future cell therapy approaches.

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