Purchase this article with an account.
Kai Postel, Tiago Santos-Ferreira, Marius Ader; Transplantation of CD73-sorted photoreceptor precursors into the rat retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5816.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Photoreceptor transplantation for the treatment of retinal degenerations is discussed as a possible therapeutic strategy. In mice enrichment and transplantation of photoreceptor precursors (PRPs) lead to integration and formation of morphological mature photoreceptors as well as restoration of vision. However, the majority of grafting experiments were conducted in mice leaving other mammalian species in regard to photoreceptor replacement not well studied. Therefore, transplantation experiments in rats were performed.
Donor rats expressing GFP under an ubiquitous promoter and host dark agouti rats were used. Magnetic activated cell sorting (MACS) with CD73 antibody was established for rat PRPs. GFP expressing and CD73 enriched rat as well as mouse PRPs, isolated at postnatal day 4 (PN4), were transplanted into the subretinal space (SRS) of adult wild type (wt) rats and mice. Integration rate of donor cells into host retinas was analysed two weeks after transplantation.
Transplantation of MACS enriched PRPs from GFP expressing mice into the retina of wt mice lead to integration of cells into the outer nuclear layer (ONL) and the formation of morphological mature photoreceptors. MACS of PN4 rat cells with CD73 antibody was established leading to enrichment of PRPs with a purity of 88%. Enriched rat PRPs were transplanted into adult mice and rats and their integration efficiency was compared with MAC-sorted mouse photoreceptors also transplanted into mice and rats. In all conditions, the majority of transplanted cells survived in the hosts’ SRS two weeks after grafting expressing photoreceptor specific markers. Whereas a significant proportion of mouse donor cells integrated into the ONL of mouse hosts, in all other conditions only a low number of cells integrated into the ONL and formed mature photoreceptors.
The difference between mouse and rat tissue as donor as well as host strongly influences the integration of transplanted PRPs. Thus, assessment of photoreceptor integration in pre-clinical animal models as well as human tissue will be crucial for evaluating the potential of photoreceptor replacement strategies. Additionally, a detailed analysis of the molecular requirements that allow successful mouse to mouse grafting and evaluation of the factors hindering photoreceptor integration in rats might be highly important for the development of cell transplantation for retinopathies.
This PDF is available to Subscribers Only