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ORIGINAL RESEARCH article

Front. Mol. Neurosci.
Sec. Brain Disease Mechanisms
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1484964

Transcorneal electrical stimulation restores DNA methylation changes in retinal degeneration

Provisionally accepted
Ben Yi Tew Ben Yi Tew 1Gerald C Gooden Gerald C Gooden 1Pei-An Lo Pei-An Lo 1Dimitrios Pollalis Dimitrios Pollalis 1Brandon Ebright Brandon Ebright 1Alex J Kalfa Alex J Kalfa 1Alejandra Gonzalez-Calle Alejandra Gonzalez-Calle 1Biju Thomas Biju Thomas 1David N Buckley David N Buckley 1Thomas Simon Thomas Simon 1Zeyi Yang Zeyi Yang 1Ege Iseri Ege Iseri 1Cody L Dunton Cody L Dunton 2Vadim Backman Vadim Backman 2Stan G. Louie Stan G. Louie 1Gianluca Lazzi Gianluca Lazzi 1Mark S. Humayun Mark S. Humayun 1Bodour Salhia Bodour Salhia 1*
  • 1 University of Southern California, Los Angeles, United States
  • 2 Northwestern University, Evanston, Illinois, United States

The final, formatted version of the article will be published soon.

    Background: Retina degeneration is a major cause of irreversible blindness. Stimulation with controlled low-level electrical fields, such as transcorneal electrical stimulation (TES), has recently been postulated as a therapeutic strategy. Despite some promising results, there is insufficient molecular characterization of the therapeutic effects of TES.Methods: Controlled, non-invasive TES was delivered using a custom contact lens electrode to the retinas of Royal College of Surgeons (RCS) rats, a model of retinal degeneration. DNA methylation in the retina, brain and blood plasma was assessed by reduced representation bisulfite sequencing (RRBS) and gene expression by RNA sequencing.Results: TES induced DNA methylation and gene expression changes implicated in neuroprotection in the retina of RCS rats. Using an epigenomic retinal health score derived from DNA methylation changes observed with disease progression in RCS rats, we showed that TES improved the epigenomic health of the retina. TES also induced DNA methylation changes in the superior colliculus: the brain region integrating visual signaling. Lastly, we demonstrated that TES-induced retinal DNA methylation changes were detectable in cell-free DNA derived from plasma.TES induces DNA methylation changes with therapeutic effects, which can be measured in circulation. These findings shed light on the therapeutic potential and molecular underpinnings of TES, and provide a foundation for the further development of TES to improve the retinal health of patients with degenerative eye diseases.

    Keywords: Retina, Retinal Degeneration, Electrical Stimulation, DNA Methylation, Epigenomics

    Received: 22 Aug 2024; Accepted: 08 Nov 2024.

    Copyright: © 2024 Tew, Gooden, Lo, Pollalis, Ebright, Kalfa, Gonzalez-Calle, Thomas, Buckley, Simon, Yang, Iseri, Dunton, Backman, Louie, Lazzi, Humayun and Salhia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Bodour Salhia, University of Southern California, Los Angeles, United States

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