Electrical Stimulation Therapy Preserves Visual Acuity And Retinal Ganglion Cells In P23H-1 Rats

Abstract

Purpose: : Low level electrical stimulation applied to the eye via retinal implants or transcorneal contact lens electrodes has been shown to be neuroprotective to degenerating retinal neurons. Here, we examined the neuroprotective effects of whole-eye electrical stimulation (WES) using silver pellet electrode on the cornea, referenced to the cheek. This method has the potential to deliver a more uniform non-invasive stimulation to the retina.

Methods: : At P28, pigmented heterozygous P23H line 1 rats were anesthetized and stimulated monocularly (n=10) with sine wave current (4 μA at 5 Hz) twice a week while non-stimulated animals served as controls (n=15). Every 4 weeks, retinal function was assessed using full-field electroretinography (ERG) with increasing flash stimuli [Scotopic (-3.4 to 3.0 log cd s/m²), Photopic (-0.8 to 2.0 log cd s/m²)] and visual acuity thresholds measured with optokinetic tracking. In stimulated animals, contralateral control eyes were omitted from the analysis due to possible co-stimulation. Animals were followed for 20 weeks post-stimulation and euthanized for histological assessment.

Results: : Scotopic b-wave amplitudes of WES eyes were significantly greater at 8 weeks (Two way RM ANOVA, p=0.028) post-stimulation but did not differ from the control group by the end of the study. Visual acuity thresholds were 10-20% higher in treated eyes across all time points (p≤0.001). Histological assessment showed significantly greater retinal ganglion cell counts (p=0.005) in WES eyes, especially in the area inferior to the optic nerve.

Conclusions: : WES has neuroprotective effects on retinal ganglion cell counts in the P23H-1 rat which may preserve visual acuity. However, WES led to only transient preservation of retinal function as measured by ERG. Retinal ganglion cells may be particularly receptive to neuroprotective effects of low level electrical stimulation.

Keywords: electroretinography: non-clinical • retinal degenerations: cell biology • neuroprotection