Introduction: Studies show that electric fields are used as therapy
during nerve and tissue injuries along with trans-retinal stimulation. However,
cellular and molecular changes induced by such treatments remain largely unknown
especially in retinal photoreceptor cells. In vitro studies show that
direct current electric fields (dcEF) were known to influence cell division,
polarity, shape, and motility. Here we could characterize for the first time the
reactions of 661W, a retinal cone photoreceptor especially regarding organelle
polarization, membrane polarization of mitochondria, O consumption, ATP/ADP
ratio and gene expression. Methods: The 661W cells were stimulated with
a constant dcEF of field strength 5 V/cm during 30 min or 5 h depending on the
parameters studied. Results: In response to dcEF, the cells aligned
perpendicular to the field by forming a leading edge with extended membrane
protrusions towards the cathode. Using immunofluorescence and live cell imaging,
we show that the cell membrane depolarized at the cathodal side. The microtubules
spread into the direction of migration. Also, the microtubule organization center
re-oriented into this direction. Concomitantly with the microtubules, actin
filaments reorganized in an asymmetrical fashion mainly at the cathodal side. The
Golgi apparatus, which is involved in many steps of actin synthesis, moved to the
cathodal side. In the last 2 h of the 5 h experiment, microtubules positioned
themselves at the rear (anodal side), like the nucleus. The averaged displacement
of the whole cells under dcEF was 155% of control for 3 V/cm and 235% for 5
V/cm. The average speed increased by 142% and 243% respectively. Inside the
cells mitochondria moved to the cathodal side, where the energy consuming
producing processes take place. In this line, we measured an increase in ATP
production and O consumption. Mitochondrial calcium was found more on the
anodal side, at the site of the nucleus with its calcium delivering endoplasmic
reticulum. In addition, oxymetry studies reveal an increased ATP synthesis by
115.2% and oxygen consumption by 113.3% 3 h after dcEF stimulation. An analysis
of differentially expressed genes by RNA sequencing revealed an upregulation of
genes involved in cellular movement, cell to cell and intracellular signaling,
molecular transport, assembly and organization. Conclusions: The
mechanisms found can enhance our understanding regarding the beneficial effects
of EF treatment in retinal diseases.