{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:17:54Z","timestamp":1787771874658,"version":"build-2784847793"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:p>JOURNAL\/nrgr\/04.03\/01300535-202411000-00034\/figure1\/v\/2026-06-18T063637Z\/r\/image-tiff<\/jats:p>\n                  <jats:p>\n                    Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors, leading to progressive photoreceptor loss. Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival. This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation (tcES) in mice affected by inherited retinal degeneration. Additionally, the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans. In this study, we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL\/6J mice using an intraocular needle probe with rectangular, sine, and ramp waveforms. To investigate the functional effects of electrical stimulation on photoreceptors, we used human retinal explant cultures and\n                    <jats:italic toggle=\"yes\">rhodopsin<\/jats:italic>\n                    knockout (\n                    <jats:italic toggle=\"yes\">Rho<\/jats:italic>\n                    <jats:sup>\u2013<\/jats:sup>\n                    <jats:sup>\/<\/jats:sup>\n                    <jats:sup>\u2013<\/jats:sup>\n                    ) mice, demonstrating progressive photoreceptor degeneration with age. Human retinal explants isolated from the donors\u2019 eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    . Photoreceptor density was evaluated by rhodopsin immunolabeling.\n                    <jats:italic toggle=\"yes\">In vivo Rho<\/jats:italic>\n                    <jats:sup>\u2013<\/jats:sup>\n                    <jats:sup>\/<\/jats:sup>\n                    <jats:sup>\u2013<\/jats:sup>\n                    mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms. Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response (OMR), respectively. Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas. Oscilloscope recordings indicated effective delivery of rectangular, sine, and ramp waveforms to the retina by transcorneal electrical stimulation, of which the ramp waveform required the lowest voltage. Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes. The temperature recordings during and after electrical stimulation indicated no significant temperature change\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    and only a subtle temperature increase\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    (~0.5\u20131.5\u00b0C). Electrical stimulation increased photoreceptor survival in human retinal explant cultures, particularly at the ramp waveform. Transcorneal electrical stimulation (rectangular + ramp) waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results. Histology and immunolabeling demonstrated increased photoreceptor survival, improved outer nuclear layer thickness, and increased bipolar cell sprouting in\n                    <jats:italic toggle=\"yes\">Rho<\/jats:italic>\n                    <jats:sup>\u2013<\/jats:sup>\n                    <jats:sup>\/<\/jats:sup>\n                    <jats:sup>\u2013<\/jats:sup>\n                    mice. These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina, improves photoreceptor survival in both human and mouse retinas, and increases visual function in\n                    <jats:italic toggle=\"yes\">Rho<\/jats:italic>\n                    <jats:sup>\u2013<\/jats:sup>\n                    <jats:sup>\/<\/jats:sup>\n                    <jats:sup>\u2013<\/jats:sup>\n                    mice. Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion.\n                  <\/jats:p>","DOI":"10.4103\/1673-5374.392888","type":"journal-article","created":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T08:00:50Z","timestamp":1707811250000},"page":"2543-2552","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":8,"title":["Optimal transcorneal electrical stimulation parameters for preserving photoreceptors in a mouse model of retinitis pigmentosa"],"prefix":"10.4103","volume":"19","author":[{"given":"Sam","family":"Enayati","sequence":"first","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA"},{"name":"Institute of clinical medicine, Faculty of Medicine, University of Oslo, Oslo, Norway"},{"name":"Department of Medical Biochemistry, Oslo University Hospital, University of Oslo, Oslo, Norway"},{"name":"Department of Ophthalmology, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Chang","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA"},{"name":"Department of Medical Biochemistry, Oslo University Hospital, University of Oslo, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Lennikov","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA"},{"name":"Department of Medical Biochemistry, Oslo University Hospital, University of Oslo, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menglu","family":"Yang","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cherin","family":"Lee","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Ashok","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA"},{"name":"Department of Medical Biochemistry, Oslo University Hospital, University of Oslo, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farris","family":"Elzaridi","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Yen","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasim","family":"Gunes","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA"},{"name":"Department of Histology and Embryology, School of Medicine, Marmara University, Istanbul, Turkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Xie","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kin-Sang","family":"Cho","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tor Paaske","family":"Utheim","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA"},{"name":"Institute of clinical medicine, Faculty of Medicine, University of Oslo, Oslo, Norway"},{"name":"Department of Medical Biochemistry, Oslo University Hospital, University of Oslo, Oslo, Norway"},{"name":"Department of Ophthalmology, Drammen Hospital, Vestre Viken Hospital Trust, Drammen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6283-8843","authenticated-orcid":false,"given":"Dong Feng","family":"Chen","sequence":"additional","affiliation":[{"name":"Schepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,1,8]]},"reference":[{"key":"R1-20260618","doi-asserted-by":"crossref","first-page":"1059020","DOI":"10.3389\/fendo.2023.1059020","article-title":"Fibroblast growth factor 21 is expressed and secreted from skeletal muscle following electrical stimulation via extracellular ATP activation of the PI3K\/Akt\/mTOR signaling pathway","volume":"14","author":"Arias-Calderon","year":"2023","journal-title":"Front Endocrinol 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