Optimizing photoreceptor materials transfer efficiency by modulating the donor-host contact interface

Abstract

Purpose : Retinal degeneration can cause severe vision loss. There is no cure for most patients due to the diverse genes involved in pathogenesis. Recently finding of inter-photoreceptor materials transfer holds promise for the development of therapeutic approaches. However, the relatively low transfer efficiency may pose a potential roadblock to clinical translation. Based on the mechanism of photoreceptor material transfer that requires cell-cell contact, we aimed to study the role of donor-host cell lay contact in promoting materials transfer efficiency.

Methods : We transplanted NRL-GFP⁺ photoreceptors (post-natal day 3-6) into adult host mice (ROSA nT/nG). We used two approaches to facilitate donor-host contact: 1. Cell concentration approach: increase donor cell density at the donor-host interface by increasing donor cell quantity with fixed bolus volume; 2. Cell distribution approach: increase the contact interface between donor and host cell layers by increasing the bolus volume with fixed donor cell quantity. In the Approach 1, we transplanted high-density (4x10^{^6} cells/1.5µL) or low-density (2x10^{^5} cells/1.5µL) doses per eye. In the Approach 2, we transplanted large-volume (2x10^{^5} cells/4.5µL) or small-volume (2x10^{^5} cells/1.5 µL) doses per eye. Three weeks post-transplantation, histological assay was performed to quantify the GFP transfer efficiency. We define GFP transfer efficiency as the ratio of host-GFP⁺ photoreceptors to host photoreceptors in the transplanted area.

Results : The data showed greater GFP transfer efficiency in the high-concentration group (5.6%) than in the low-concentration group (2.2%), an increase in transfer efficiency of approximately 2.5 times. The large-volume group showed very low GFP transfer efficiency (approximately 0.25%) and this was associated with very low donor cell survival post-transplantation. The GFP transfer efficiency in recipient rod photoreceptors (7.2%) was greater than in recipient cone photoreceptors (1.5%).

Conclusions : The study suggests that a greater density of donor cells at the donor-host interface may promote transfer efficiency. Materials transfer has the potential to repair both rod and cone photoreceptors. The relationship between donor cell concentration, bolus volume, and materials transfer efficiency should be studied further as a potential means to optimize material transfer efficiency in the context of clinical translation.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.