AUTHOR=Rajendran Nair Deepthi S. , Gupta Anika , Iseri Ege , Wei Tianyuan , Phuong Quach Le Tam , Seiler Magdalene J. , Lazzi Gianluca , Thomas Biju B. TITLE=Extrinsic electric field modulates neuronal development and increases photoreceptor population in retinal organoids JOURNAL=Frontiers in Neuroscience VOLUME=Volume 18 - 2024 YEAR=2024 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1438903 DOI=10.3389/fnins.2024.1438903 ISSN=1662-453X ABSTRACT=IntroductionConsidering 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.MethodsRetinal organoids derived from human embryonic stem cells were used at day 80, a key stage in their differentiation. A single 60-minute exposure to a biphasic electrical field was administered to assess its influence on retinal cell populations and maturation markers. Immunohistochemistry, qPCR, and RNA sequencing were employed to evaluate cell type development and gene expression changes.ResultsElectrical stimulation significantly enhanced neuronal development and increased the population of photoreceptors within the organoids. RNA sequencing data showed upregulated expression of genes related to rod photoreceptors, Müller cells, horizontal cells, and amacrine cells, while genes associated with retinal pigment epithelium and retinal ganglion cells were downregulated. Variations in development and maturation were observed depending on the specific parameters of the applied electric field.DiscussionThese findings highlight the significant impact of extrinsic electrical fields on early retinal development and suggest that optimizing electrical field parameters could effectively address certain limitations in retinal organoid technology, potentially reducing the reliance on chemicals and small molecules.