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Kimberly Gokoffski, Min Zhao; Electical Fields Direct Retinal Ganglion Cell Axon Growth. Invest. Ophthalmol. Vis. Sci. 2019;60(9):644.
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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. Current cell transplantation based approaches are limited by poor integration efficiency and failure of surviving RGCs to extend an axon out of the eye. Instead, axons were confined to the retina. What these experiments demonstrate is that the endogenous cues in the host retina and optic nerve are insufficient to direct the growth of newly transplanted RGC axons out of the eye.There is much interest in the potential of electrical fields (EFs) to promote long distance axonal growth. The body has naturally occurring electrical currents and EFs have been shown to direct the growth axons of hippocampal and peripheral neurons. Drawing from this, we hypothesized that EFs exert a similar galvanotropic effect on RGC axon growth.
Full thickness retina was isolated from post-natal mice and cultured in an electrotaxis apparatus. Retina was then exposed to varying EF strengths. Time-lapsed microscopy was performed and videos used to quantify the direction and rate of axon growth.
In the absence of an EF, RGC axons 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 to the cathode, while 4.8% and 14.1% were directed to the anode or perpendicular to the field, respectively (p<0.001). Interestingly, RGC axons retained the ability to respond to acute changes in EF polarity by changing their direction of growth: in response to a 180 degree switch, 78% of axons redirected growth towards the “new” cathode, 36% towards the “new” anode, while 14% did not react to the switch in EF polarity. This turning was more frequent than the random turns seen in control cultures (36% to right, 39% to left, 25% no change; p<0.0001). Of the axons that rerouted their growth towards the “new” cathode, 56% were observed to have done so within 45 minutes of changing EF polarity.
Here, we demonstrate that RGC axons exhibit directional growth when exposed to an EF. The acuity with which RGC axons respond to changes in EF polarity suggests that the effect of EFs on RGCs is direct. The significance of this work lies in its potential to advance the field of optic nerve regeneration. Furture animal studies will help determine whether application of EFs is sufficient to direct the growth of newly transplanted RGCs.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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