Dynamic Transcriptomic Remodeling in Human Neural Progenitor Cells Reveals Mechanisms for Vision Preservation in Retinitis Pigmentosa Model

Human neural progenitor cells (hNPCs) have shown promise in slowing down retinal degeneration in animal models and are currently being tested in clinical trials for treating retinitis pigmentosa (RP). However, the status of grafted hNPCs and their interaction with host retinal cells over time is largely unknown. Here, we investigated single-cell transcriptomic changes in grafted hNPCs and host retinal cells following injection into a rodent model for RP. Grafted hNPCs and host retinal cells undergo dynamic transcriptomic changes in the degenerative retinal environment. Grafted hNPCs protect vision through multiple mechanisms, including trophic factor support, modulation of metabolic activity, reduction of apoptosis, oxidative stress, and inflammation, alongside extracellular matrix remodeling. CellChat analysis revealed a progressive decline in intercellular signaling and communication strength between hNPCs and host retinal cells over time. This study indicates that enhancing trophic factor supports and improving host retinal environment are key targets to enable long-term vision preservation.