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Madalena Carido, Yu Zhu, Boris Benkner, Thomas Kurth, Thomas Munch, Elly Tanaka, Marius Ader; Transplantation of Human ESC-derived RPE into Rodent Models of Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5838.
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Cell-based therapies are among the suggested options for retinal degeneration diseases, and aim for the replacement of the degenerating cell population. Here we focus on the potential effects of human embryonic stem cells (hESC)-derived retinal pigment epithelium (RPE) upon transplantation into two rodent models of retinal degeneration caused by RPE loss or malfunction. Particularly, we are interested in assessing cell survival, rescue effect and functionality.
Highly pure RPE cells differentiated in vitro from hES cells were transplanted into the subretinal space of P19-21 RCS rats and adult wild-type C57BL/6 mice previously treated with sodium iodate (NaIO3) to induce retinal degeneration. Control retinae were either transplanted with human fibroblasts, sham-injected (PBS) or left untreated. 3 or 6 weeks post transplantation (NaIO3 mice and RCS rats, respectively) the retinae were isolated and processed for immunohistochemical and ultrastructural evaluation. Functional characterization was done by electroretinography (ERG) (both models) and by measuring visual acuity with an optomotor drum (NaIO3 mice).
Transplanted hES-derived RPE cells were found up to 6 weeks post transplantation, mainly around the injection site. In addtion, several donor cells integrated into the host RPE layer (RCS rats) or formed a monolayer with up to 1650μm in length on the free Bruch’s membrane (NaIO3 mice). Interestingly, transplanted cells show a correct polarization and are connected via tight junctions. Importantly, in both models the outer nuclear layer is significantly thicker after transplantation of RPE cells in comparison to untreated controls. Interestingly, donor RPE cells grafted in NaIO3 mice showed ability to phagocyte shed outer segments. Nevertheless, no difference was detected between transplanted and control eyes at the level of ERG nor optokinetic tracking, with no significant response recorded with any of the methods.
Transplanted RPE cells are able to survive in the host environment and show protective effects detected at the morphological level. The exact mechanism of the observed protection is not yet fully understood, since also fibroblasts have a protective effect, slowing the degeneration process in RCS rats. However, the observed morphological rescue is not accompanied by a rescue at the functional level.
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