Abstract
Purpose :
Neurons transmit electrical signals and communicate with other cells through electrical activities. Electrical stimulation (ES) has been shown to have therapeutic potential for diseases in the nervous system, including the retina, by improving cell survival and function. The neuroprotective and regenerative potential of ES was investigated in a mouse model of inherited retinal degeneration. We investigated the effects of ES on microglia and photoreceptor cells in a mouse model of inherited retinal degeneration.
Methods :
Rhodopsin-deficient (Rho−/−) mice received sham or transpalpebral ES at a biphasic Ramp or Rectangular waveform (100 µA), respectively, starting at 6 weeks of age. To determine the optimal frequencies of ES sessions, mice were divided into three groups: group 1 received everyday ES, group 2 was treated every other day, and group 3 was treated every 3 days. The Sham group received treatments every day without ES. During each session, the ES probe was placed for 1 minute per spot on the skin around the mouse orbit—two on the upper eyelid and two on the lower eyelid. Mouse spatial vision, including visual acuity and contrast sensitivity, was determined using optomotor response (OMR) assays and electroretinography (ERG) was performed to evaluate retinal functions. The mice were sacrificed at the endpoint. Microglia and cone photoreceptors in retinal sections were counted. Immunohistochemistry was used to assess retinal morphology, microglia activation, and photoreceptor survival in vivo.
Results :
Non-invasive transpalpebral ES in Rho−/− mice improved photoreceptor survival as well as OMR-based spatial vision and ERG responses, particularly in mice received ES every other day at a ramp waveform. IBA1+ and CD68+ microglial cells were clearly observed in the outer plexiform layer (OPL), outer nuclear layer (ONL), and subretinal space (SRS) of Rho−/− mice, but significantly reduced in number and density in the ONL and SRS of mice received ES every other day at a ramp waveform, as compared to vehicle control mice.
Conclusions :
Transpalpebral ES treatment inhibits microglial activation and promotes photoreceptor survival in Rho−/− mice, a mouse model of inherited retinal degeneration. These results suggest the exciting possibility of applying ES as a versatile tool for preventing photoreceptor and vision loss in patients with photoreceptor degeneration.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.