Extrinsic electric field modulates neuronal development and increases photoreceptor population in retinal organoids

Deepthi S Rajendran Nair; Anika Gupta; Ege Iseri; Tianyuan Wei; Le Tam Phuong Quach; Magdalene J Seiler; Gianluca Lazzi; Biju B Thomas

doi:10.3389/fnins.2024.1438903

Extrinsic electric field modulates neuronal development and increases photoreceptor population in retinal organoids

Front Neurosci. 2024 Nov 29:18:1438903. doi: 10.3389/fnins.2024.1438903. eCollection 2024.

Authors

Deepthi S Rajendran Nair¹, Anika Gupta¹, Ege Iseri², Tianyuan Wei², Le Tam Phuong Quach¹, Magdalene J Seiler^{3

4}, Gianluca Lazzi^{5

6}, Biju B Thomas^{1

6}

Affiliations

¹ Department of Ophthalmology, USC Roski Eye Institute, University of Southern California, Los Angeles, CA, United States.
² Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, United States.
³ Departments of Physical Medicine and Rehabilitation; Ophthalmology; Anatomy and Neurobiology, University of California, Irvine, Irvine, CA, United States.
⁴ Stem Cell Research Center, University of California, Irvine, Irvine, CA, United States.
⁵ Department of Electrical and Computer Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA, United States.
⁶ USC Ginsburg Institute for Biomedical Therapeutics, University of Southern California, Los Angeles, CA, United States.

Abstract

Introduction: 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.

Methods: Retinal 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.

Results: Electrical 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.

Discussion: These 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.

Keywords: electrical field; electrical stimulation; photoreceptors; retinal degeneration; retinal organoids; stem cell differentiation.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by CIRMDISC1-09912 (BT), NIHEY031144 (BT). R01 EY031834 (MJS, BT), R01 EY 017337 from the National Eye Institute, National Institute of Health, Bethesda, Maryland, USA., The authors acknowledge departmental support from a Research to Prevent Blindness (RPB, New York, NY, United States) unrestricted grant to the UCI Department of Ophthalmology. This study was supported by NIHP30EY029220 (USC Ophthalmology Core grant), an unrestricted grant to the USC Department of Ophthalmology and grants from the National Science Foundation under Grant Nos 1933394, 2121164.