Sammendrag
Non-invasive electrical stimulation (ES) is increasingly applied to improve vision in
untreatable eye conditions, such as retinitis pigmentosa and age-related macular degeneration. Our
previous study suggested that ES promoted retinal function and the proliferation of progenitor-like
glial cells in mice with inherited photoreceptor degeneration; however, the underlying mechanism
remains obscure. Müller cells (MCs) are thought to be dormant residential progenitor cells that possess
a high potential for retinal neuron repair and functional plasticity. Here, we showed that ES with a
ramp waveform of 20 Hz and 300 µA of current was effective at inducing mouse MC proliferation and
enhancing their expression of progenitor cell markers, such as Crx (cone–rod homeobox) and Wnt7,
as well as their production of trophic factors, including ciliary neurotrophic factor. RNA sequencing
revealed that calcium signaling pathway activation was a key event, with a false discovery rate of
5.33 × 10−8
(p = 1.78 × 10−10) in ES-mediated gene profiling changes. Moreover, the calcium channel
blocker, nifedipine, abolished the observed effects of ES on MC proliferation and progenitor cell gene
induction, supporting a central role of ES-induced Ca2+ signaling in the MC changes. Our results
suggest that low-current ES may present a convenient tool for manipulating MC behavior toward
neuroregeneration and repair.
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