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Michael D Andrews, Jonathan Stoddard, Nir Netzer, Osnat Bohana-Kashtan, Charles Irving, Neelay Pandit, Eyal Banin, Benjamin Reubinoff, Mark E Pennesi, Trevor J McGill; Long Term Efficacy of Xeno-free hESC-derived RPE Cells Following Transplantation into Royal College of Surgeons Rats. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1275.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal degenerative diseases (RDD) affect millions of people worldwide resulting in progressive and permanent vision loss. To evaluate long-term efficacy, retinal pigmented epithelial (RPE) cells derived from a xeno-free clinical grade human embryonic stem cell source were transplanted into the sub-retinal space of the Royal College of Surgeons (RCS) rats. Subsequent evaluations included quantification of visual function preservation, an assessment of transplanted cell survival and function (phagocytosis), local migration, and quantification of rod and cone photoreceptor rescue.
Post-natal day (P) 20-25 RCS rats (n=236) received subretinal injection of a single cell transplant of 25,000 (low), 100,000 (mid), or 200,000 (high) OpRegen RPE cells, BSS+ (vehicle control), or were unoperated controls. Fundus photography was used to confirm successful delivery of cells/vehicle into the subretinal space. Four survival groups were examined P60, P100, P150, and P200. Optomotor tracking and electroretinography (ERG) were used to confirm functional efficacy. Cross-sectional histology and immunohistochemistry were used to confirm structural rescue and transplanted cell survival and function.
Optomotor testing revealed that cell treated eyes outperformed vehicle injected or unoperated eyes at all ages. Both mid and high cell-dosed eyes significantly outperformed the low dose, but were not significantly different from one another. ERG testing revealed select cell treated animals that significantly outperformed control or fellow eyes in both focal and full-field ERGs independent of dose. Cell treated eyes had significantly thicker outer nuclear layers than controls up to P150, however no significant difference was observed at P200. Transplanted OpRegen RPE cells were identified in all age groups, generated a monolayer and demonstrated the ability to phagocytose rat rhodopsin.
When transplanted into the subretinal space of RCS rats, OpRegen RPE cells rescued visual acuity, ERG b-wave amplitudes, and rod and cone photoreceptors within close proximity to the grafted cells. Therefore, OpRegen RPE cells appear to have significant potential for the treatment of human RPE cell disorders such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD).
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