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Kimberly Kinga Gokoffski, Xingyuan Jia, Min Zhao; Electrical Fields Direct Retina Ganglion Cell Neurite Growth. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3752. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Restoration of vision in patients blinded by optic neuropathies requires regenerating the optic nerve. Intraocular transplantation of retinal ganglion cells (RGCs) alone is insufficient to regenerate the optic nerve due to failure to sustain axon growth and/or insufficient directional cues. There is much interest in the potential role of electrical fields (EFs) in promoting long distance axon growth. Motor neuron and dorsal root ganglion cell axons have been shown to grow directionally when exposed to an EF. Whether EFs can direct RGC axon growth is unknown, as are the mechanisms through which EFs mediate directional growth. Members of the Rho Kinase signaling pathway have been shown to meditate EF-induced directional growth of spinal nerves. We hypothesize that EFs direct and sustain RGC neurite growth by signaling through the Rho kinase pathway.
Post-natal retina was cultured in an electrotaxis apparatus and then exposed to varying EF strengths with/without ToxinB, a non-specific inhibitor of Rho Kinase signaling. Time-lapsed microscopy was performed and videos used to quantify the direction and rate of neurite growth.
In the absence of an EF, RGC neurites demonstrated indiscriminate directional growth from the tissue edge. Retinal cultures that were exposed to an EF of 200mV/mm, however, showed marked asymmetric growth: 81.2% were directed at the cathode, while 4.8% and 14.1% were directed towards the anode or perpendicular to the field, respectively (p<0.001). EF did not affect the rate of RGC axon growth. Interestingly, RGC axons retain their ability to respond to acute changes in EF polarity by changing their direction of growth. Finally, ToxinB neutralized EF-induced (200mV/mm) directional growth of retinal neurites. However, when the field strength was increased to 270mV/mm and 350mV/mm, directional growth was restored.
Here, we demonstrate that RGC neurites exhibit directional growth when exposed to an EF. The acuity with which RGC neurites respond to changes in EF polarity suggests that the effect of EFs on RGCs is direct. Additionally, our data suggest that Rho Kinase signaling is necessary to translate EFs into directional cues in RGC neurites. The significance of this work lies in its potential to advance the field of optic nerve regeneration. Application of electrical currents may be necessary to direct the growth of newly transplanted RGCs.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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