Noninvasive Electrical Stimulation As a Neuroprotective strategy in Retinal Diseases: a Systematic Review of Preclinical Studies

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2024 Jan 6

PMID 38184580

Authors

Jiaxian Li

Wei Zhou

Lina Liang

Yamin Li

Kai Xu

Xiaoyu Li

Ziyang Huang

Yu Jin

Affiliations

Soon will be listed here.

Abstract

Background: Electrical activity has a crucial impact on the development and survival of neurons. Numerous recent studies have shown that noninvasive electrical stimulation (NES) has neuroprotective action in various retinal disorders.

Objective: To systematically review the literature on in vivo studies and provide a comprehensive summary of the neuroprotective action and the mechanisms of NES on retinal disorders.

Methods: Based on the PRISMA guideline, a systematic review was conducted in PubMed, Web of Science, Embase, Scopus and Cochrane Library to collect all relevant in vivo studies on "the role of NES on retinal diseases" published up until September 2023. Possible biases were identified with the adopted SYRCLE's tool.

Results: Of the 791 initially gathered studies, 21 articles met inclusion/exclusion criteria for full-text review. The results revealed the neuroprotective effect of NES (involved whole-eye, transcorneal, transscleral, transpalpebral, transorbital electrical stimulation) on different retinal diseases, including retinitis pigmentosa, retinal degeneration, high-intraocular pressure injury, traumatic optic neuropathy, nonarteritic ischemic optic neuropathy. NES could effectively delay degeneration and apoptosis of retinal neurons, preserve retinal structure and visual function with high security, and its mechanism of action might be related to promoting the secretion of neurotrophins and growth factors, decreasing inflammation, inhibiting apoptosis. The quality scores of included studies ranged from 5 to 8 points (a total of 10 points), according to SYRCLE's risk of bias tool.

Conclusion: This systematic review indicated that NES exerts neuroprotective effects on retinal disease models mainly through its neurotrophic, anti-inflammatory, and anti-apoptotic capabilities. To assess the efficacy of NES in a therapeutic setting, however, well-designed clinical trials are required in the future.

Citing Articles

An exploratory study to evaluate efficacy and safety of frequent Transcutaneous Electrical Stimulation for Leber Hereditary Optic Neuropathy.

Takano F, Ueda K, Kurimoto T, Arai M, Nagai T, Yamada-Nakanishi Y Sci Rep. 2025; 15(1):4829.

PMID: 39924552 PMC: 11808102. DOI: 10.1038/s41598-025-89076-z.

Optic nerve-mediated modulation of temporally interfering electric fields for potential targeted retinal disease therapy: a computational modeling study.

Zhou M, Su X, Guo T, Meng T, Wu W, Di L Front Neurosci. 2025; 18:1518488.

PMID: 39764387 PMC: 11701049. DOI: 10.3389/fnins.2024.1518488.

Preservation of vision by transpalpebral electrical stimulation in mice with inherited retinal degeneration.

Gunes K, Chang K, Lennikov A, Tai W, Chen J, ElZaridi F Front Cell Dev Biol. 2024; 12:1412909.

PMID: 39206091 PMC: 11349514. DOI: 10.3389/fcell.2024.1412909.

Diabetes mellitus, hearing loss, and therapeutic interventions: A systematic review of insights from preclinical animal models.

Mittal R, Keith G, Lacey M, Lemos J, Mittal J, Assayed A PLoS One. 2024; 19(7):e0305617.

PMID: 38985787 PMC: 11236185. DOI: 10.1371/journal.pone.0305617.

Chronic electrical stimulation with a peripheral suprachoroidal retinal implant: a preclinical safety study of neuroprotective stimulation.

Abbott C, Allen P, Williams C, Williams R, Epp S, Burns O Front Cell Dev Biol. 2024; 12:1422764.

PMID: 38966426 PMC: 11222648. DOI: 10.3389/fcell.2024.1422764.

References

Shepherd R, Shivdasani M, Nayagam D, Williams C, Blamey P . Visual prostheses for the blind. Trends Biotechnol. 2013; 31(10):562-71. DOI: 10.1016/j.tibtech.2013.07.001. View

Yang M, Lennikov A, Chang K, Ashok A, Lee C, Cho K . Transcorneal but not transpalpebral electrical stimulation disrupts mucin homeostasis of the ocular surface. BMC Ophthalmol. 2022; 22(1):490. PMC: 9756492. DOI: 10.1186/s12886-022-02717-z. View

Schatz A, Rock T, Naycheva L, Willmann G, Wilhelm B, Peters T . Transcorneal electrical stimulation for patients with retinitis pigmentosa: a prospective, randomized, sham-controlled exploratory study. Invest Ophthalmol Vis Sci. 2011; 52(7):4485-96. DOI: 10.1167/iovs.10-6932. View

Fujii M, Sunagawa G, Kondo M, Takahashi M, Mandai M . Evaluation of micro Electroretinograms Recorded with Multiple Electrode Array to Assess Focal Retinal Function. Sci Rep. 2016; 6:30719. PMC: 4969741. DOI: 10.1038/srep30719. View

Rodriguez Villanueva J, Martin Esteban J, Rodriguez Villanueva L . Retinal Cell Protection in Ocular Excitotoxicity Diseases. Possible Alternatives Offered by Microparticulate Drug Delivery Systems and Future Prospects. Pharmaceutics. 2020; 12(2). PMC: 7076407. DOI: 10.3390/pharmaceutics12020094. View

Yu W, Tse A, Guan L, Chiu J, Tan S, Khairuddin S . Antidepressant-like effects of transcorneal electrical stimulation in rat models. Brain Stimul. 2022; 15(3):843-856. DOI: 10.1016/j.brs.2022.05.018. View

Morimoto T, Kanda H, Kondo M, Terasaki H, Nishida K, Fujikado T . Transcorneal electrical stimulation promotes survival of photoreceptors and improves retinal function in rhodopsin P347L transgenic rabbits. Invest Ophthalmol Vis Sci. 2012; 53(7):4254-61. DOI: 10.1167/iovs.11-9067. View

Osako T, Chuman H, Maekubo T, Ishiai M, Kawano N, Nao-I N . Effects of steroid administration and transcorneal electrical stimulation on the anatomic and electrophysiologic deterioration of nonarteritic ischemic optic neuropathy in a rodent model. Jpn J Ophthalmol. 2013; 57(4):410-5. DOI: 10.1007/s10384-012-0203-y. View

Kanamoto T, Souchelnytskyi N, Kurimoto T, Ikeda Y, Sakaue H, Munemasa Y . Proteomic study of retinal proteins associated with transcorneal electric stimulation in rats. J Ophthalmol. 2015; 2015:492050. PMC: 4364380. DOI: 10.1155/2015/492050. View

10.

Liu F, Liu X, Zhou Y, Yu Y, Wang K, Zhou Z . Wolfberry-derived zeaxanthin dipalmitate delays retinal degeneration in a mouse model of retinitis pigmentosa through modulating STAT3, CCL2 and MAPK pathways. J Neurochem. 2021; 158(5):1131-1150. DOI: 10.1111/jnc.15472. View

11.

Perin C, Vigano B, Piscitelli D, Matteo B, Meroni R, Cerri C . Non-invasive current stimulation in vision recovery: a review of the literature. Restor Neurol Neurosci. 2019; 38(3):239-250. PMC: 7504999. DOI: 10.3233/RNN-190948. View

12.

Willmann G, Schaferhoff K, Fischer M, Arango-Gonzalez B, Bolz S, Naycheva L . Gene expression profiling of the retina after transcorneal electrical stimulation in wild-type Brown Norway rats. Invest Ophthalmol Vis Sci. 2011; 52(10):7529-37. DOI: 10.1167/iovs.11-7838. View

13.

Oono S, Kurimoto T, Kashimoto R, Tagami Y, Okamoto N, Mimura O . Transcorneal electrical stimulation improves visual function in eyes with branch retinal artery occlusion. Clin Ophthalmol. 2011; 5:397-402. PMC: 3076113. DOI: 10.2147/OPTH.S17751. View

14.

Reinhart R, Xiao W, McClenahan L, Woodman G . Electrical Stimulation of Visual Cortex Can Immediately Improve Spatial Vision. Curr Biol. 2016; 26(14):1867-72. PMC: 4961578. DOI: 10.1016/j.cub.2016.05.019. View

15.

Bellapianta A, Cetkovic A, Bolz M, Salti A . Retinal Organoids and Retinal Prostheses: An Overview. Int J Mol Sci. 2022; 23(6). PMC: 8953078. DOI: 10.3390/ijms23062922. View

16.

Hill D, Compagnoni C, Cordeiro M . Investigational neuroprotective compounds in clinical trials for retinal disease. Expert Opin Investig Drugs. 2021; 30(5):571-577. DOI: 10.1080/13543784.2021.1896701. View

17.

Adenzato M, Manenti R, Enrici I, Gobbi E, Brambilla M, Alberici A . Transcranial direct current stimulation enhances theory of mind in Parkinson's disease patients with mild cognitive impairment: a randomized, double-blind, sham-controlled study. Transl Neurodegener. 2019; 8:1. PMC: 6322239. DOI: 10.1186/s40035-018-0141-9. View

18.

Morimoto T, Miyoshi T, Sawai H, Fujikado T . Optimal parameters of transcorneal electrical stimulation (TES) to be neuroprotective of axotomized RGCs in adult rats. Exp Eye Res. 2009; 90(2):285-91. DOI: 10.1016/j.exer.2009.11.002. View

19.

Tao Y, Chen T, Liu B, Wang L, Peng G, Qin L . The transcorneal electrical stimulation as a novel therapeutic strategy against retinal and optic neuropathy: a review of experimental and clinical trials. Int J Ophthalmol. 2016; 9(6):914-9. PMC: 4916152. DOI: 10.18240/ijo.2016.06.21. View

20.

Tagami Y, Kurimoto T, Miyoshi T, Morimoto T, Sawai H, Mimura O . Axonal regeneration induced by repetitive electrical stimulation of crushed optic nerve in adult rats. Jpn J Ophthalmol. 2009; 53(3):257-66. DOI: 10.1007/s10384-009-0657-8. View