Tran-sclera electrical stimulation protects degenerated retina in rd10 mice

Abstract

Purpose: Retinitis pigmentosa (RP) is a hereditary blinding disease characterized by degeneration of photoreceptors. Trans-corneal electrical stimulation has shown neuroprotective effects in degenerated retina, but repeated application causes injury on cornea. Here we tested whether repetitive trans-sclera electrical stimulation (TsES) may protect degenerated retina in rd10 mice, a model of RP, without corneal damage. Methods: At postnatal day 20 (P20) after rods starts to degenerate, right eyes of rd10 mice were exposed to 30 minutes TsES daily or every other day till P25 when rods apoptosis reach peak. The stimuli was 20Hz square-wave with amplitude of either 50 or 100 μA and width of 2.5ms. Mice receiving zero current stimulation served as control. Immunostaining and multi-electrode-array (MEA) recording was applied to examine the morphological and functional changes of treated retina. Results: Our preliminary data showed that TsES improved the survival of photoreceptors in rd10 mice. The abnormal high spontaneous firing of rd10 retinal ganglion cells (RGCs) was greatly reduced after TsES. Though the light responses of rd10 RGCs were still low, TsES increased their light sensitivities as well as the signal-to-noise ratio. Micro-electroretinogram data further showed an enhancement of photoreceptor response to light. The functional improvement was better when using 100 μA electrical stimulation than 50 μA, and when treated every other day than daily treatment. Conclusions: Our data suggests that repetitive TsES protects the degenerated retina in rd10 mice, both morphologically and functionally. Therefore it might be an effective long-term strategy to delay the retinal degeneration in RP patients. Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details. In photoreceptor degenerated disease such as retinitis pigmentosa (RP), patients lose their vision and become blind, but there is no effective treatment so far. Electric-stimulation on cornea has demonstrated protective effects in degenerated retina, but repeated application causes injury on cornea. To avoid this, we used trans-sclera electrical stimulation instead, and tested its effect on a transgenic mouse with photoreceptor degeneration. We found that repetitive trans-sclera electrical stimulation effectively protects the degenerated retina, both morphologically and functionally. Therefore it might be an effective long-term strategy to delay the retinal degeneration in RP patients.