Retinoic acid drives cell fate specification, maturation and retinal regionality in human retinal organoids [Visium]

Despite its well-established role in retinal patterning, the concentration-dependent effects of RA on human retinal cell fate specification and the regional definition of the primate macula and peripheral retina remain poorly understood.

Here, we show that temporal and dosage-dependant modulation of RA during human retinal organoid differentiation induces distinct changes in retinal cell abundance, maturation, and organisation. Single-cell transcriptomics and protein analysis revealed that RA dosage influenced the relative abundance and maturation of photoreceptors and retinal interneurons. Spatial transcriptomics analyses demonstrated that low RA levels biased retinal organoids toward a macular-like regional identity, whereas high RA levels promoted peripheral-like development.