Noninvasive electrical stimulation as a neuroprotective strategy in retinal diseases: a systematic review of preclinical studies

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.

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

“…Low level electrical stimulation is believed to protect the retina from degeneration ( Morimoto, 2012 ; Pardue et al, 2014 ). Preclinical model and clinical studies suggest that low level electrical stimulation is effective for retinal and optic nerve diseases such as glaucoma, AMD and RP ( Morimoto et al, 2007 ; Morimoto et al, 2010 ; Schatz et al, 2011 ; Bittner and Seger, 2018 ; Shen et al, 2021 ; Parkinson et al, 2023 ; Stett et al, 2023 ; Li et al, 2024 ). A systematic review of the clinical literature suggests electrical stimulation has “promising therapeutic effects on RP and optic neuropathy” although indicates that “more large-scale randomized controlled trial studies should be conducted to elucidate the potential of electrical stimulation, especially on AMD, retinal artery occlusion and glaucoma” ( Liu et al, 2021 ).…”