{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:52:19Z","timestamp":1789908739257,"version":"4.0.1"},"reference-count":39,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,17]],"date-time":"2022-11-17T00:00:00Z","timestamp":1668643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Midstream Research Programme for Universities, Hong Kong","award":["MRP-092-17x"],"award-info":[{"award-number":["MRP-092-17x"]}]},{"name":"Midstream Research Programme for Universities, Hong Kong","award":["2018B030332001"],"award-info":[{"award-number":["2018B030332001"]}]},{"name":"Midstream Research Programme for Universities, Hong Kong","award":["20200730009"],"award-info":[{"award-number":["20200730009"]}]},{"name":"Guangdong Grant Key Technologies for Treatment of Brain Disorders, China","award":["MRP-092-17x"],"award-info":[{"award-number":["MRP-092-17x"]}]},{"name":"Guangdong Grant Key Technologies for Treatment of Brain Disorders, China","award":["2018B030332001"],"award-info":[{"award-number":["2018B030332001"]}]},{"name":"Guangdong Grant Key Technologies for Treatment of Brain Disorders, China","award":["20200730009"],"award-info":[{"award-number":["20200730009"]}]},{"name":"Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology","award":["MRP-092-17x"],"award-info":[{"award-number":["MRP-092-17x"]}]},{"name":"Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology","award":["2018B030332001"],"award-info":[{"award-number":["2018B030332001"]}]},{"name":"Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology","award":["20200730009"],"award-info":[{"award-number":["20200730009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Retinitis pigmentosa (RP) is a photoreceptor-degenerating disease with no effective treatment. Trans-corneal electrical stimulation has neuroprotective effects in degenerating retinas, but repeated applications cause corneal injury. To avoid the risk of corneal damage, here we tested whether repetitive trans-sclera electrical stimulation (TsES) protects degenerating retinas in rd10 mice, a model of RP. At postnatal day 20 (P20), the right eyes of rd10 mice were exposed to 30 min of TsES daily or every other day till P25, at the amplitude of 50 or 100 \u03bcA, with zero current as the sham. Immunostaining, multi-electrode-array (MEA) recording, and a black-and-white transition box were applied to examine the morphological and functional changes of the treated retina. Functionally, TsES modified the retinal light responses. It also reduced the high spontaneous firing of retinal ganglion cells. TsES at 100 \u03bcA but not 50 \u03bcA increased the light sensitivities of ganglion cells as well as their signal-to-noise ratios. TsES at 100 \u03bcA increased the survival of photoreceptors without improving the visual behavior of rd10 mice. Our data suggest that repetitive TsES improves the retinal function of rd10 mice at the early degenerating stage, therefore, it might be an effective long-term strategy to delay retinal degeneration in RP patients.<\/jats:p>","DOI":"10.3390\/life12111917","type":"journal-article","created":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T03:35:23Z","timestamp":1668742523000},"page":"1917","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Trans-Sclera Electrical Stimulation Improves Retinal Function in a Mouse Model of Retinitis Pigmentosa"],"prefix":"10.3390","volume":"12","author":[{"given":"Feng","family":"Liu","sequence":"first","affiliation":[{"name":"Guangdong-Hongkong-Macau Institute of CNS Regeneration, Key Laboratory of CNS Regeneration (Ministry of Education), Jinan University, 601 West Huangpu Ave., Guangzhou 510632, China"},{"name":"State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengrong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong-Hongkong-Macau Institute of CNS Regeneration, Key Laboratory of CNS Regeneration (Ministry of Education), Jinan University, 601 West Huangpu Ave., Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyin","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu","family":"Han","sequence":"additional","affiliation":[{"name":"Guangdong-Hongkong-Macau Institute of CNS Regeneration, Key Laboratory of CNS Regeneration (Ministry of Education), Jinan University, 601 West Huangpu Ave., Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwok-Fai","family":"So","sequence":"additional","affiliation":[{"name":"Guangdong-Hongkong-Macau Institute of CNS Regeneration, Key Laboratory of CNS Regeneration (Ministry of Education), Jinan University, 601 West Huangpu Ave., Guangzhou 510632, China"},{"name":"Department of Ophthalmology, The University of Hong Kong, Hong Kong SAR, China"},{"name":"Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226019, China"},{"name":"The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, China"},{"name":"Department of Psychology, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kin","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The University of Hong Kong, Hong Kong SAR, China"},{"name":"The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, China"},{"name":"Department of Psychology, The University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9987-2057","authenticated-orcid":false,"given":"Ying","family":"Xu","sequence":"additional","affiliation":[{"name":"Guangdong-Hongkong-Macau Institute of CNS Regeneration, Key Laboratory of CNS Regeneration (Ministry of Education), Jinan University, 601 West Huangpu Ave., Guangzhou 510632, China"},{"name":"Co-Innovation Center of Neuroregeneration, Nantong University, Nantong 226019, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1750-1172-1-40","article-title":"Retinitis pigmentosa","volume":"1","author":"Hamel","year":"2006","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.preteyeres.2018.03.005","article-title":"Non-syndromic retinitis pigmentosa","volume":"66","author":"Verbakel","year":"2018","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Gallenga, C.E., Lonardi, M., Pacetti, S., Violanti, S.S., Tassinari, P., Di Virgilio, F., Tognon, M., and Perri, P. (2021). Molecular Mechanisms Related to Oxidative Stress in Retinitis Pigmentosa. Antioxid, 10.","DOI":"10.3390\/antiox10060848"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Kaur, G., and Singh, N.K. (2021). The Role of Inflammation in Retinal Neurodegeneration and Degenerative Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23010386"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1111\/aos.14138","article-title":"Vascular dysfunction in retinitis pigmentosa","volume":"97","author":"Lang","year":"2019","journal-title":"Acta Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1097\/IIO.0000000000000256","article-title":"Retinitis Pigmentosa: Review of Current Treatment","volume":"59","author":"Wang","year":"2019","journal-title":"Int. Ophthalmol. Clin."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1007\/s00018-019-03446-1","article-title":"Biomedical applications of electrical stimulation","volume":"77","author":"Zhao","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1111\/ner.13414","article-title":"Effectiveness of Microcurrent Stimulation in Preserving Retinal Function of Blind Leading Retinal Degeneration and Optic Neuropathy: A Systematic Review","volume":"24","author":"Liu","year":"2021","journal-title":"Neuromodulation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4725","DOI":"10.1167\/iovs.06-1404","article-title":"Transcorneal electrical stimulation promotes the survival of photoreceptors and preserves retinal function in royal college of surgeons rats","volume":"48","author":"Morimoto","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.expneurol.2009.06.016","article-title":"Neuroprotective effect of transcorneal electrical stimulation on light-induced photoreceptor degeneration","volume":"219","author":"Ni","year":"2009","journal-title":"Exp. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4614","DOI":"10.1167\/iovs.16-19305","article-title":"Topographic Quantification of the Transcorneal Electrical Stimulation (TES)-Induced Protective Effects on N-Methyl-N-Nitrosourea-Treated Retinas","volume":"57","author":"Tao","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4254","DOI":"10.1167\/iovs.11-9067","article-title":"Transcorneal electrical stimulation promotes survival of photoreceptors and improves retinal function in rhodopsin P347L transgenic rabbits","volume":"53","author":"Morimoto","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.visres.2012.10.016","article-title":"Chronic delivery of low-level exogenous current preserves retinal function in pigmented P23H rat","volume":"76","author":"Rahmani","year":"2013","journal-title":"Vision Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"572299","DOI":"10.3389\/fnins.2020.572299","article-title":"Excitation of the Pre-frontal and Primary Visual Cortex in Response to Transcorneal Electrical Stimulation in Retinal Degeneration Mice","volume":"14","author":"Agadagba","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"897","DOI":"10.2147\/OPTH.S204669","article-title":"A study protocol for evaluating the efficacy and safety of skin electrical stimulation for Leber hereditary optic neuropathy: A single-arm, open-label, non-randomized prospective exploratory study","volume":"13","author":"Kurimoto","year":"2019","journal-title":"Clin. Ophthalmol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.neuroscience.2008.06.042","article-title":"Functional and structural modifications during retinal degeneration in the rd10 mouse","volume":"155","author":"Barhoum","year":"2008","journal-title":"Neuroscience"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"120585","DOI":"10.1016\/j.biomaterials.2020.120585","article-title":"Electrical stimulation at nanoscale topography boosts neural stem cell neurogenesis through the enhancement of autophagy signaling","volume":"268","author":"He","year":"2021","journal-title":"Biomaterials"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Liu, J., Ma, A.K.H., So, K.F., Lee, V.W.H., and Chiu, K. (2022). Mechanisms of electrical stimulation in eye diseases: A narrative review. Adv. Ophthalmol. Pract. Res., 2.","DOI":"10.1016\/j.aopr.2022.100060"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1111\/jnc.15472","article-title":"Wolfberry-derived zeaxanthin dipalmitate delays retinal degeneration in a mouse model of retinitis pigmentosa through modulating STAT3, CCL2 and MAPK pathways","volume":"158","author":"Liu","year":"2021","journal-title":"J. Neurochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"30719","DOI":"10.1038\/srep30719","article-title":"Evaluation of micro Electroretinograms Recorded with Multiple Electrode Array to Assess Focal Retinal Function","volume":"6","author":"Fujii","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"330","DOI":"10.3389\/fncel.2015.00330","article-title":"Blockade of pathological retinal ganglion cell hyperactivity improves optogenetically evoked light responses in rd1 mice","volume":"9","author":"Barrett","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"13972","DOI":"10.1523\/JNEUROSCI.2399-13.2013","article-title":"Block of gap junctions eliminates aberrant activity and restores light responses during retinal degeneration","volume":"33","author":"Toychiev","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1988","DOI":"10.1167\/iovs.12-10706","article-title":"Visual signal pathway reorganization in the Cacna1f mutant rat model","volume":"54","author":"Tao","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3579","DOI":"10.1167\/iovs.05-1450","article-title":"Visual response properties of retinal ganglion cells in the royal college of surgeons dystrophic rat","volume":"47","author":"Pu","year":"2006","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.exer.2016.06.010","article-title":"Whole-eye electrical stimulation therapy preserves visual function and structure in P23H-1 rats","volume":"149","author":"Hanif","year":"2016","journal-title":"Exp. Eye Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5552","DOI":"10.1167\/iovs.12-10037","article-title":"Transcorneal Electrical Stimulation Shows Neuroprotective Effects in Retinas of Light-Exposed Rats","volume":"53","author":"Schatz","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_27","first-page":"914","article-title":"The transcorneal electrical stimulation as a novel therapeutic strategy against retinal and optic neuropathy: A review of experimental and clinical trials","volume":"9","author":"Tao","year":"2016","journal-title":"Int. J. Ophthalmol"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"492050","DOI":"10.1155\/2015\/492050","article-title":"Proteomic Study of Retinal Proteins Associated with Transcorneal Electric Stimulation in Rats","volume":"2015","author":"Kanamoto","year":"2015","journal-title":"J. Ophthalmol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.exer.2009.11.002","article-title":"Optimal parameters of transcorneal electrical stimulation (TES) to be neuroprotective of axotomized RGCs in adult rats","volume":"90","author":"Morimoto","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1167\/iovs.18-25156","article-title":"Viability of Mouse Retinal Explant Cultures Assessed by Preservation of Functionality and Morphology","volume":"60","author":"Alarautalahti","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/s42003-020-01594-w","article-title":"Optogenetic therapy: High spatiotemporal resolution and pattern discrimination compatible with vision restoration in non-human primates","volume":"4","author":"Gauvain","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1038\/s42003-022-04016-1","article-title":"Bipolar cell targeted optogenetic gene therapy restores parallel retinal signaling and high-level vision in the degenerated retina","volume":"5","author":"Kralik","year":"2022","journal-title":"Commun. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/nn.2117","article-title":"Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration","volume":"11","author":"Lagali","year":"2008","journal-title":"Nat. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2598","DOI":"10.1172\/JCI92156","article-title":"Photopharmacological control of bipolar cells restores visual function in blind mice","volume":"127","author":"Laprell","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"28086","DOI":"10.1038\/srep28086","article-title":"Characterisation of light responses in the retina of mice lacking principle components of rod, cone and melanopsin phototransduction signalling pathways","volume":"6","author":"Hughes","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"320","DOI":"10.3389\/fnins.2019.00320","article-title":"N(3)-MEA Probes: Scooping Neuronal Networks","volume":"13","author":"Kireev","year":"2019","journal-title":"Front. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kralik, J., and Kleinlogel, S. (2021). Functional Availability of ON-Bipolar Cells in the Degenerated Retina: Timing and Longevity of an Optogenetic Gene Therapy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222111515"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"5653","DOI":"10.1167\/iovs.12-9678","article-title":"Flash responses of mouse rod photoreceptors in the isolated retina and corneal electroretinogram: Comparison of gain and kinetics","volume":"53","author":"Heikkinen","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Donato, L., Scimone, C., Alibrandi, S., Abdalla, E.M., Nabil, K.M., D\u2019Angelo, R., and Sidoti, A. (2020). New Omics-Derived Perspectives on Retinal Dystrophies: Could Ion Channels-Encoding or Related Genes Act as Modifier of Pathological Phenotype?. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010070"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/11\/1917\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:20:38Z","timestamp":1760145638000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/12\/11\/1917"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,17]]},"references-count":39,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["life12111917"],"URL":"https:\/\/doi.org\/10.3390\/life12111917","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,17]]}}}