Transcorneal electrical stimulation restores DNA methylation changes in retinal degeneration

BackgroundRetinal 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. With promising results, there is a need for detailed molecula...

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Bibliographic Details
Published in:Frontiers in molecular neuroscience 2024-12, Vol.17
Main Authors: Ben Yi Tew, Gerald C. Gooden, Pei-An Lo, Dimitrios Pollalis, Brandon Ebright, Alex J. Kalfa, Alejandra Gonzalez-Calle, Biju Thomas, David N. Buckley, Thomas Simon, Zeyi Yang, Ege Iseri, Cody L. Dunton, Vadim Backman, Stan Louie, Gianluca Lazzi, Mark S. Humayun, Bodour Salhia
Format: Article
Language:English
Subjects:
DNA methylation
electrical stimulation
epigenomics
retina
retinal degeneration
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Summary:BackgroundRetinal 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. With promising results, there is a need for detailed molecular characterization of the therapeutic effects of TES.MethodsControlled, 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 cell-free DNA in plasma was assessed by reduced representation bisulfite sequencing (RRBS) and gene expression by RNA sequencing.ResultsTES induced DNA methylation and gene expression changes implicated in neuroprotection in the retina of RCS rats. We devised an epigenomic-based retinal health score, derived from DNA methylation changes observed with disease progression in RCS rats, and showed that TES improved the epigenomic health of the retina. TES also induced DNA methylation changes in the superior colliculus: the brain which is involved in integrating visual signaling. Lastly, we demonstrated that TES-induced retinal DNA methylation changes were detectable in cell-free DNA derived from plasma.ConclusionTES induced DNA methylation changes with therapeutic effects, which can be measured in circulation. Based on these changes, we were able to devise a liquid biopsy biomarker for retinal health. 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.
ISSN:1662-5099
DOI:10.3389/fnmol.2024.1484964