Abstract
Purpose :
Subretinal transplantation of human neural stem cell (hNSC) clusters has been associated with slowed progression of geographic atrophy in age-related macular degeneration (AMD) patients. The main goals of this study were to improve the hNSC product by developing a single-cell suspension formulation and to quantify its neuroprotective efficacy in the RCS rat.
Methods :
RCS rats were treated at postnatal day 21 (P21) in one eye with either a single-cell suspension or a cell cluster formulation of hNSCs at a dose of 150,000 cells in a 2 μL subretinal injection. The contralateral control eye was left unoperated or injected with balanced salt solution. Optokinetic tracking (OKT) was evaluated at P60, P90, P180 and P240 to measure preservation of visual performance. Whole globes were harvested at P60, P90, and P240 for immunofluorescence (IF) using a marker specific for human cells (STEM121) and a nuclear counterstain (DAPI) to determine the presence of cells. Outer nuclear layer (ONL) thickness was quantified in the retinal cross-sections.
Results :
At P60, IF showed a clear presence of STEM121-positive cells in the subretinal space. The ONL was thicker in treated areas of the retina where transplanted cells were present. Outside of treated areas, the retina showed progressive photoreceptor degeneration. OKT data showed consistently better visual performance in the treated eyes compared with contralateral control eyes at P60.
Conclusions :
A novel single-cell suspension of hNSCs with high cell viability was successfully generated and showed neuroprotection in the RCS rat. This product may be able to improve hNSC transplantation treatments for AMD eyes with geographic atrophy.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.