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.

PURPOSE. Neurons carry electrical signals and communicate via electrical activities. The therapeutic potential of electrical stimulation (ES) for the nervous system, including the retina, through improvement of cell survival and function has been noted. Here we investigated the neuroprotective and regenerative potential of ES in a mouse model of inherited retinal degeneration. METHODS. Rhodopsin-deficient (Rho −/−) mice received one or two sessions of transpalpebral ES or sham treatments for 7 consecutive days. Intraperitoneal injection of 5-ethynyl-2-deoxyuridine was used to label proliferating cells. Weekly electroretinograms were performed to monitor retinal function. Retinal morphology, photoreceptor survival, and regeneration were evaluated in vivo using immunohistochemistry and genetic fatemapping techniques. Müller cell (MC) cultures were employed to further define the optimal conditions of ES application. RESULTS. Noninvasive transpalpebral ES in Rho −/− mice improved photoreceptor survival and electroretinography function in vivo. ES also triggered residential retinal progenitorlike cells such as MCs to reenter the cell cycle, possibly producing new photoreceptors, as shown by immunohistochemistry and genetic fate-mapping techniques. ES directly stimulated cell proliferation and the expression of progenitor cell markers in MC cultures, at least partially through bFGF signaling. CONCLUSIONS. Our study showed that transpalpebral ES improved photoreceptor survival and retinal function and induced the proliferation, probably photoreceptor regeneration, of MCs; this occurs via stimulation of the bFGF pathways. These results suggest the exciting possibility of applying noninvasive ES as a versatile tool for preventing photoreceptor loss and mobilizing endogenous progenitors for reversing vision loss in patients with photoreceptor degeneration.

Purpose: To investigate the incidence of rhegmatogenous retinal detachment (RRD) and describe characteristics of the RRD population. Methods: Retrospective, observational case series. Data on residents of South Rogaland, Norway, diagnosed with primary RRD in the period 2000-2019 were obtained by medical chart review. Patient demographics and prior intraocular surgery were documented. Incidence rates adjusted to the Norwegian population were calculated for 5-year periods and stratified by age, sex and lens status. Results: The RRD incidence increased from 12.6 per 100 000 person-years in 2000-2004 to 20.2 in 2015-2019. The RRD incidence increased by 2.9% per year (p < 0.0001) corresponding to an accumulated increase of 77%. Demographic changes accounted for 30% of the increase. The pseudophakic RRD incidence increased yearly by 4.9% (p < 0.0001), over double the rate of the phakic RRD increase of 2.3% (p = 0.0005). In individuals ≥50 years old, the annual RRD incidence increase was 4.5% (p = 0.019) for pseudophakic females, 3.9% (p = 0.001) for pseudophakic males and 2.6% (p = 0.03) for phakic females. Males were younger compared with females when undergoing lens exchange surgery, 58.5 (SD 12.5) versus 62.4 (SD 13.2) years, (p = 0.013) and when diagnosed with pseudophakic RRD, 61.9 (SD 12.5) versus 68.2 (SD 12.9) years, (p < 0.0001). There was no significant increase in subjects under 50 years of age. Conclusion:The RRD incidence increased dramatically over 20 years, of which 30% was attributed to demographic changes. The most pronounced change occurred in pseudophakic RRD, which calls for raised awareness of the individual risk related to lens exchange surgery.