Therapeutic Evaluation of the Suprachoroidal Space for Stem Cell Delivery in Retinal Degeneration.

The route of administration is a crucial determinant of the success of stem cell-based therapies, especially in intraocular applications. It significantly influences therapeutic outcomes and the risk of adverse events. We aimed to evaluate the utility of the suprachoroidal space (SCS) as a delivery route for human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) in a rabbit model of retinal degeneration in comparison with the intravitreal (IVT) route. A custom-designed, three-dimensional-printed needle cap was employed to ensure precise hESC-MSC delivery into the SCS via a relatively less invasive approach. Green fluorescent protein (GFP)-induced hESC-MSC expression was monitored for 7 weeks to assess persistence and localization. Therapeutic potential was assessed using electroretinography (ERG) as well as histological and immunofluorescence examinations on Day 28. Flourscence signals were still detectable up to Week 2, which indicated precise delivery to the posterior segment of the eye. There were significant ERG improvements in the hESC-MSC-treated group compared with those in the phosphate-buffered saline-treated group. Furthermore, the hESC-MSC-treated group showed a significant increase in outer nuclear layer thickness and cell number, as well as upregulated rhodopsin and opsin expression. Additionally, there was minimal inflammation in SC-injected eyes compared with that in IVT-injected eyes on Day 14. Our findings highlight the potential of the SCS as an optimal route for hESC-MSC delivery. Specifically, it allows retinal targeting that significantly enhances visual function restoration while minimizing adverse events.