Rapid developmental changes in retinal organoids after brief exposure to extrinsic electrical fields

Abstract Considering the significant role played by both intrinsic and extrinsic electric fields in the growth and maturation of the central nervous system, the impact of short exposure to external electric fields on the development and differentiation of retinal organoids was investigated. Organoids derived from human embryonic stem cells at day 80, a critical time point in their differentiation and maturation, were used. A single 60-minute exposure to distinct biphasic electrical fields expedited the commitment and maturation of the photoreceptor lineage. Morphology, qPCR, and RNA sequencing data revealed elevated expression of rod photoreceptors, muller cells, horizontal cells, and amacrine cells, alongside the downregulation of retinal pigment epithelium and retinal ganglion cell genes. Furthermore, our study demonstrated varying degrees of organoid development and maturation depending on the specific electrical field applied. These findings provide valuable insights into the profound influence of extrinsic electrical fields on early retinal development and emphasize that several existing limitations in retinal organoid technology can be easily overcome by using suitable electrical field parameters without applying chemicals and small molecules.