Neuroprotective Effect of Non-Invasive Electrical Stimulation in Mice with Inherited Retinal Disease

Abstract

Purpose : The potential neuroprotective and regenerative properties of Electrical Stimulation (ES) were explored in rhodopsin knockout mice (Rho^-/-), a murine model of inherited retinal degeneration. The study focused on assessing the impact of treatment frequencies of ES on both visual behavioral tests and photoreceptor cell survival in Rho^-/- mice. The primary objective is to elucidate the impact of electrical stimulation on the survival of cones, crucial photoreceptors responsible for daylight vision.

Methods : Rho-/- mice received either sham or transpalpebral ES using a biphasic Ramp waveform (100 µA) starting at six weeks of age. The treatment duration spanned either one week or three weeks. To determine the optimal treatment frequency of ES sessions, mice were divided into three groups: group 1 received daily ES, group 2 was treated every other day, and group 3 received treatment every three days. The Sham group received daily treatments without the application of ES. The visual function of the mice was assessed at baseline (before ES), one week, two weeks, and three weeks after the first ES session using Optomotor Response (OMR) assays. Subsequently, mice were sacrificed, and retinal tissues were immunolabeled for Peanut agglutinin (PNA) and quantified for cone survival.

Results : Our findings reveal significant improvement in visual function in Rho^-/-mice following non-invasive every day or every other day transpalpebral ES, as evidenced by OMR assays. Concurrently, immunohistochemistry for PNA demonstrates a pronounced increase in the survival of cones. Molecular analyses further unveil the modulation of critical markers associated with cone survival, providing insights into the underlying neuroprotective mechanisms activated by ES.

Conclusions : This study underscores the neuroprotective effect of non-invasive ES in rhodopsin knockout-induced retinal degenerative disorders, mainly retinitis pigmentosa. The observed enhancement in visual function and significant rescue of cones position ES as a promising therapeutic strategy for treating photoreceptor degeneration. These findings hold translational significance, providing a foundation for developing targeted therapeutic interventions for individuals facing the challenges of rhodopsin-associated retinal degeneration, with potential implications extending to personalized and effective treatments for retinitis pigmentosa.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.