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Ma'ayan Semo, Aisling Lynch, Nasrin Haamedi, David Carter, John Sinden, Michael Young, Lara Stevanato, Sara Patel, Anthony Vugler; Transplantation of human retinal progenitor cells into the P23H rat improves the scotopic ERG.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1821.
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© ARVO (1962-2015); The Authors (2016-present)
The P23H rat is a model of human autosomal dominant retinitis pigmentosa. Here we investigate the potential of a clinical grade human retinal progenitor cell (hRPC) line to improve or preserve vision in this model following an established tolerization protocol.
The hRPC line used in this study (GS089) was derived from human fetal retina, obtained in compliance with the procedures of The European Union Tissues and Cells Directive (EUCTD), The UK Human Tissue Act and USA 21 Code of Federal Regulations Part 1271. The hRPCs were manufactured under GMP conditions and banked at passage 8. Cryopreserved cells were then cultured and formulated as drug product, passage 9.<br /> On the day of birth (postnatal day 0 (P0)), heterozygote P23H rat pups received a single intra peritoneal injection of hRPCs (5X104 in 1μl). From P21 onwards the rats were administered 210mg/L oral cyclosporine. At P24-25 the left eye received an intravitreal injection of hRPCs (5X104 in 2μl, n=8) or vehicle (HBSS-NAC, n=8). At P53-57 simultaneous bilateral electroretinogram (ERG) recordings of scotopic and photopic visual function was performed, using the Diagnosys system and Espion software. At P61-63, rats were perfused and their eyes were processed for immunofluorescence.
The raw scotopic and photopic ERG data did not reveal any significant effect of transplantation. However, as simultaneous bilateral ERGs were recorded, within animal (left eye - right eye) corrections were made. This revealed a subtle but significant improvement in the scotopic a- (by -6 µV) and b-wave (by 34 µV) amplitudes at the highest light intensity tested (28 cd/s/m2). The vehicle treatment consistently reduced b-wave amplitude significantly (by -19 µV) at the lowest light intensity tested (0.3x10-3 cd/s/m2). At P61-63 very few surviving hRPCs were detected in the transplanted eyes, however auto-fluorescent macrophage activity was clearly present.
The intravitreal transplantion of hRPCs improved the scotopic ERG in the P23H rat. The mechanism for this may be linked to neuroprotective factors released by the hRPCs prior to rejection and/or the protective effects of the host inflammatory/immune response to the xenograft. Importantly, the tolerization protocol employed here was ineffective in preventing rejection of hRPCs.
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