Whole-eye electrical stimulation therapy preserves visual function and structure in P23H-1 rats

Abstract

Low-level electrical stimulation to the eye has been shown to be neuroprotective against retinal degeneration in both human and animal subjects, using approaches such as subretinal implants and transcorneal electrical stimulation. In this study, we investigated the benefits of whole-eye electrical stimulation (WES) in a rodent model of retinitis pigmentosa. Transgenic rats with a P23H-1 rhodopsin mutation were treated with 30 min of low-level electrical stimulation (4 μA at 5 Hz; n = 10) or sham stimulation (Sham group; n = 15), twice per week, from 4 to 24 weeks of age. Retinal and visual functions were assessed every 4 weeks using electroretinography and optokinetic tracking, respectively. At the final time point, eyes were enucleated and processed for histology. Separate cohorts were stimulated once for 30 min, and retinal tissue harvested at 1 h and 24 h post-stimulation for real-time PCR detection of growth factors and inflammatory and apoptotic markers. At all time-points after treatment, WES-treated rat eyes exhibited significantly higher spatial frequency thresholds than untreated eyes. Inner retinal function, as measured by ERG oscillatory potentials (OPs), showed significantly improved OP amplitudes at 8 and 12 weeks post-WES compared to Sham eyes. Additionally, while photoreceptor segment and nuclei thicknesses in P23H-1 rats did not change between treatment groups, WES-treated eyes had significantly greater numbers of retinal ganglion cell nuclei than Sham eyes at 20 weeks post-WES. Gene expression levels of brain-derived neurotrophic factor (BDNF), caspase 3, fibroblast growth factor 2 (FGF2), and glutamine synthetase (GS) were significantly higher at 1 h, but not 24 h after WES treatment. Our findings suggest that WES has a beneficial effect on visual function in a rat model of retinal degeneration and that post-receptoral neurons may be particularly responsive to electrical stimulation therapy.

Mesenchymal stem cell surgery, rescue and regeneration in retinitis pigmentosa: clinical and rehabilitative prognostic aspects

“…While the methods of Electrical Stimulation (ES) administration are different, their influence on the preservation of retinal structure and function is similar and based on studies in animal models. In the rat model of retinitis pigmentosa (RP), it has been shown that ES preserved outer nuclear layer (ONL) thickness and delayed inner retinal degeneration (Manthey et al, 2017;Hanif et al, 2016).…”

Transcorneal Electrical Stimulation for the Treatment of Retinitis Pigmentosa: A Multicenter Safety Study of the OkuStim® System (TESOLA-Study)

“…Cell biology studies of TES have found alterations in the expression of a wide variety of retinal genes and altogether there is no indication of a single dominant target. Genes covering cell regulation, immunity, cell communication, and cell differentiation have been implicated [12,13]. The patients in the present study were not routinely tested for the causative genetic mutation nor selected for any specific genotype, but this may be a significant factor in predicting the success of the therapy.…”

“…Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is thought to have a critical neuroprotective role in retinal disease as well as other central nervous system conditions such as Parkinson's disease [16] and deserves further attention. BDNF is involved in the survival of retinal pigment epithelium cells [16] and has been shown to alter following TES [5,13,17]. BDNF is able to cross the blood -retinal barrier, which may limit the usefulness of using the contralateral eye as control eye.…”

“…BDNF is able to cross the blood -retinal barrier, which may limit the usefulness of using the contralateral eye as control eye. Although animal studies have not shown altered regulation of BDNF in the contralateral eye [13], they performed their assays after very short-term stimulation so cumulative effects of multiple treatments were not assessed. Retinal ganglion cells have been shown to have increased survival rates following TES [18,19].…”

Transient Vision Restoration Training Using a Unique Virtual Reality Platform in Glaucoma

“…Some efforts had been made to restore the residual vision for optic neuritis, ischemic neuropathy, glaucoma, photoreceptor degeneration, trauma and other neuropathies [10,[13][14][15][16]. Besides, very few reports have been published that visual restoration in patients with glaucoma may be achieved using the repetitive transorbital alternating current stimulation (rtACS) [17][18][19].…”