Abstract
Purpose :
The purpose of this study was to determine whether a combined therapy with retinal precursor cells (RPC) together with retinal pigment epithelial (RPE) cells, derived from hiPSC, can preserve retinal structure and function better that RPE cell therapy, currently used in clinics, in a RCS rat model.
Methods :
RPC and RPE cells expressing GFP were obtained from hiPSC. Three groups of RCS rats (p21) were subretinally injected through the trans-scleral route with a cell suspension of PRE cells (105 cell/eye; n=14), with a combination of RPE cells and RPC (5x104 cells/eye each cell type; n=23) and with medium (n=9). Eyes were in vivo monitored for 12 weeks by fluorescence fundus imaging, optical coherence tomography (OCT) and scotopic electroretinogram (ERG). At 1, 8 and 12 weeks, eyes were analyzed by IHC and H&E.
Results :
hiPSC-RPE cells expressed specific markers and phagocyted POS in vitro. hiPSC-RPC at day 45 of differentiation mostly comprised photoreceptor precursors expressing CRX, NRL and RAX markers. Upon transplantation, fluorescent images and OCT showed that transplanted cells were placed into the subretinal space and survived 12 weeks. Rats treated with the combination of RPC and RPE cells exhibited a significant conservation of ONL (p<0.005), compared with rats treated with RPE cells or medium. This conservation was also correlated with an improved visual preservation, showing better b-wave and a-wave responses, and short implicit time (p<0.005). Engrafted RPE cells integrated in the host RPE layer while RPC mostly remained in the subretinal space, although some cells integrated in the ONL. Despite that, eyes treated with the combined RPC and RPE cell therapy better conserved ONL which extended beyond the grafted cell area, suggesting a neuroprotective effect of transplanted cells rather than a replacement.
Conclusions :
These data demonstrate that the transplantation a combination of hiPSC-derived RPE cells and RPC is potentially better therapeutic approach to preserve retina from degeneration and to conserve visual function in advanced stages of retinal degenerative diseases
This is a 2020 ARVO Annual Meeting abstract.