A18: Characterisation of cells suitable for photoreceptor replacement

Project leader: Dr. M. Ader

Impairment of vision and blindness due to loss of photoreceptors, the light-sensitive cells of the retina, are one of the most prevalent causes of disability in industrialized countries. The adult mammalian retina lacks endogenous repair mechanisms and thus is unable to regenerate photoreceptors lost due to injury or inherited diseases.
Cell transplantation into the retina might be one possible treatment option to replace degenerating photoreceptor cells. Recently successful integration and differentiation into rod photoreceptors following transplantation into adult mouse retinas was demonstrated when primary retinal cells isolated at the peak of rod photoreceptor generation were used for grafting (Figure 1). Data implicates that retinal cells committed to the photoreceptor lineage rather then stem/progenitor cells have the greatest potential for integration into host tissue and photoreceptor differentiation. Aim of the project is to define in detail the characteristics of cells that are able to form mature photoreceptors following retinal transplantation.

Primary retinal cells isolated at postnatal day 4 from transgenic mice ubiquitously expressing EGFP were transplanted into the subretinal space of adult wild-type mice (A). Donor cells integrated into the outer nuclear layer (ONL) of the host retina and developed the specific morphology of mature photoreceptors (B) including outer- and inner segments at the apical side, a small cell body located in the ONL and axonal terminals in the outer plexiform layer (OPL) that were in close proximity to endogenous PKC-positive bipolar cells (C; arrows). Abbreviations: INL: inner nuclear layer; IS: inner segments; ONL: outer nuclear layer; OPL: outer plexiform layer; OS: outer segments. A: adopted from Eberle, 2009; B, C: adopted from Bartsch et al., 2008.