Effect of Electrical Stimulation on Ocular Cells: A Means for Improving Ocular Tissue Engineering and Treatments of Eye Diseases

Abstract

Tissue engineering is biomedical engineering that uses suitable biochemical and physicochemical factors to assemble functional constructs that restore or improve damaged tissues. Recently, cell therapies as a subset of tissue engineering have been very promising in the treatment of ocular diseases. One of the most important biophysical factors to make this happen is noninvasive electrical stimulation (ES) to target ocular cells that may preserve vision in multiple retinal and optic nerve diseases. The science of cellular and biophysical interactions is very exciting in regenerative medicine now. Although the exact effect of ES on cells is unknown, multiple mechanisms are considered to underlie the effects of ES, including increased production of neurotrophic agents, improved cell migration, and inhibition of proinflammatory cytokines and cellular apoptosis. In this review, we highlighted the effects of ES on ocular cells, especially on the corneal, retinal, and optic nerve cells. Initially, we summarized the current literature on the in vitro and in vivo effects of ES on ocular cells and then we provided the clinical studies describing the effect of ES on ocular complications. For each area, we used some of the most impactful articles to show the important concepts and results that advanced the state of these interactions. We conclude with reflections on emerging new areas and perspectives for future development in this field.

Direct modulation of microglial function by electrical field

“…Non-invasive electric stimulation (ES) is emerging as a therapeutic modality for eye and brain diseases ( Sanie-Jahromi et al, 2021 ). Clinical studies suggested that ES improves retinal function in eye diseases, such as retinitis pigmentosa ( Schatz et al, 2017 ), age-related macular degeneration (AMD) ( Shinoda et al, 2008 ), and central or branch retinal arterial occlusion ( Naycheva et al, 2013 ).…”

A narrative review of cortical visual prosthesis systems: the latest progress and significance of nanotechnology for the future

“…Next, electrical stimulation will be created to evoke visual impressions. Weekly testing will be conducted for a period of 1 to 3 years (79).…”

Bioelectric Potential in Next-Generation Organoids: Electrical Stimulation to Enhance 3D Structures of the Central Nervous System

“…The parameters of electrical stimulation, namely waveform, intensity, frequency and duration can be varied according to purpose. Numerous studies demonstrate EF modulation to target the CNS both in vivo in animal models, clinical studies, or in vitro in cell cultures ( Sehic et al, 2016 ; Bertucci et al, 2019 ; Lancaster, 2019 ; Mobini et al, 2019 ; Krauss et al, 2021 ; Sanie-Jahromi et al, 2021 ). By increasing or decreasing EFs, studies have demonstrated the importance of endogenous EFs in normal development ( Levin, 2012 ; Smith et al, 2018 ; Iwasa et al, 2019 ; Sefton et al, 2020 ; Levin, 2021 ).…”

“…Electrical stimulation has been applied to the retina via several modes in vivo , either targeting the retina from the front or side of the eye, non-invasively, or alternatively directly contacting the retinal tissue (sub-retinal). Non-invasive EF modulation has been demonstrated to preserve vision in diseased retina in both animal models and clinical trials (Reviewed in Sehic et al, 2016 ; Sanie-Jahromi et al, 2021 ). As with deep-brain stimulation, further studies are required to elucidate full mechanisms of action.…”

“…Control of ion flux, through manipulation of ion channels, or application of exogenous electrical stimulation, can be used to manipulate EFs both in vivo and in vitro. Meanwhile, in the field of regenerative medicine, exogenous application of low voltage electrical stimulation has been used to promote CNS regeneration, or prevent degeneration, in the clinic and experimental studies ( Fu et al, 2015 ; Sehic et al, 2016 ; Marquez-Chin and Popovic, 2020 ; Hellenbrand et al, 2021 ; Krauss et al, 2021 ; Sanie-Jahromi et al, 2021 ; Sui et al, 2021 ; Karamian et al, 2022 ). Bioengineering has interfaced with bioelectricity to deliver exogenous electrical stimulation through conductive biomaterial polymers in basic 3D models of the CNS ( Bierman-Duquette et al, 2021 ).…”