Abstract
Purpose :
Retinal pigment epithelium(RPE) transplantation offers promising therapeutic potential for retinal diseases. Polyethylene terephthalate(PET) membrane from transwells®, widely recognized as a biocompatible scaffold, has been utilized successfully in RPE cell culture and clinical transplantation trials as a cell carrier. The alterations in choroidal perfusion dynamics after such interventions remain unknown. Our study aimed to quantitatively assess choriocapillaris post subretinal xenotransplantation of RPE monolayers on PET scaffolds in naïve non-human primates.
Methods :
Human-induced pluripotent stem cells derived from human skin fibroblast cells were differentiated into RPE cells. Cultured RPE monolayers on PET transwells® were trephined into 1x2mm bullet-shape implants and transplanted into the subretinal space of naïve cynomolgus monkeys. Swept-source optical coherence tomography angiography was conducted quarterly for up to 1 year. RPE implants were delineated to segment the choriocapillaris into regions beneath the implant and the surrounding(Fig.1). Flow voids, representing non-perfusion areas, were assessed in these regions. Linear mixed models and Tukey's HSD test were used to compare flow void density(FD) over time.
Results :
Ten eyes with 37 imaging sessions were included. Post-transplantation, a notable change was observed in FD within the choriocapillaris beneath the implant(p=0.02). No notable changes in FD were observed in the surrounding. Comparison across time points revealed an elevation in FD within the choriocapillaris beneath the implant at 3-, 6-, 9-, and 12-month post-transplantation relative to pre-transplantation(all p<0.01). No significant differences emerged among these post-transplantation time points.
Conclusions :
Post-transplantation, perfusion dynamics changes were identified specifically within the choriocapillaris beneath the implant, while the surrounding was generally unaffected. Perfusion dynamics could start changing as early as at 3-month post-transplantation and remain stable subsequently. The observed perfusion change might arise from the rigid PET scaffold acting as a physical barrier between the retina and choroid. Our findings are crucial for refining RPE cell therapy, offering insights to improve outcomes and advance ocular health.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.