Abstract
Purpose :
Microcurrent electrical stimulation (ES) shows promise as a therapeutic approach due to its safety profile and non-invasive nature. This study evaluates the benefits of monophasic and biphasic rectangular waveforms in the laser-induced mouse model of choroidal neovascularization (CNV).
Methods :
The Laser CNV was induced in adult C57BL/6 mice (50 μm spot size, 50 ms, 150 mW). To test the impact of ES duration, the first two groups of mice were subjected to daily ES for 5 days at either 4 or 8 min per day, with 30 Hz monophasic rectangular waveform at 100 μA on days 1 – 3 and 20 Hz biphasic rectangular waveform on days 4 – 5. To determine the effects of individual ES waveforms, two additional groups of mice were subjected to daily 4 min ES with either 5 days of 30 Hz monophasic or 20 Hz biphasic rectangular waveform at 100 μA. Naïve and sham ES mice served as controls. The outcome measures included fluorescent angiography (FA), optical coherence tomography (OCT), spatial vision measured by the optometric response (OMR), quantification of IBA-1 and VEGFa immunolabelling in RPE-choroidal whole-mounts.
Results :
Combined monophasic and biphasic waveforms significantly ameliorated laser-induced CNV, as evidenced by reduced lesion size measured by OCT, FA and IBA1-positive microglial infiltration (p<0.001). OMR revealed significant improvement of visual function in mice received either 4 or 8 min ES sessions. Mice that received 4 min ES, but not 8 min ES, exhibited significantly decreased VEGFa expression compared to the control group, otherwise, no significant differences were observed between 4- and 8-min ES groups. Remarkably, all mice that received ES, monophasic or biphasic, individually or in combination, exhibited significant vision improvement as measured by OMR, as compared to sham. After 5 days of biphasic ES, significant improvements were observed across all measured outcomes compared to sham control group. These included OCT, FA, IBA-1, VEGFa immunolabeling, OMR assessment. Monophasic ES displayed trends toward reduced FA-spot size and VEGFa immunolabeling.
Conclusions :
Both combined and individual monophasic and biphasic ES ameliorate laser CNV-induced vision loss in mice. The effect does not scale with an increase in stimulation time. Additional research is required to determine if similar results may be gained in a nonexudative model.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.