@article{a6164f8eb5284cd4a8595eb26ba4554f,
title = "3D visualization of individual regenerating retinal ganglion cell axons reveals surprisingly complex growth paths",
abstract = "Retinal ganglion cells (RGCs), the sole output cells of the retina, are a heterogeneous population of neurons that project axons to visual targets in the brain. Like most CNS neurons, RGCs are considered incapable of mounting long distance axon regeneration. Using immunolabeling-enabled 3D imaging of solvent-cleared organs (iDISCO) in transgenic mice, we tracked the entire paths of individual RGC axons and show that adult RGCs are highly capable of spontaneous long-distance regeneration, even without any treatment. Our results show that the Thy1-H-YFP mouse sparsely labels RGCs, consisting predominantly of regeneration-competent α-type RGCs (αRGCs). Following optic nerve crush, many of the YFP-labeled RGC axons extend considerable distances proximal to the injury site with only a few penetrating through the lesion. This tortuous axon growth proximal to the lesion site is even more striking with intravitreal ciliary neurotrophic factor (CNTF) treatment. We further demonstrate that despite traveling more than 5 mm (i.e., a distance equal to the length of mouse optic nerve), many of these circuitous axons are confined to the injury area and fail to reach the brain. Our results re-evaluate the view that RGCs are naturally incapable of re-extending long axons, and shift the focus from promoting axon elongation, to understanding factors that prevent direct growth of axons through the lesion and the injured nerve.",
keywords = "Axon, CNS, Clearing, IDISCO, RGC, Regeneration",
author = "Bray, {Eric R.} and Markus Noga and Kinjal Thakor and Yunfang Wang and Lemmon, {Vance P.} and Park, {Kevin K.} and Pantelis Tsoulfas",
note = "Funding Information: We thank Pingping Jia at the University of Miami Viral Vector Core and Melissa Carballosa-Gautam at the Miami Project. Funding Information: This work was supported by grants from the National Eye Institute 1R01EY022961-01 (to K.K.P.), NEI 1R21EY026668-01 (to K.K.P.), NEI 1U01EY027257-01 (to K.K.P. and V.P.L.), NEI 1F30EY025527-01 (to E.R.B.), Walter G Ross Foundation (V.P.L.), Ziegler Foundation (K.K.P.), Glaucoma Research Foundation and Pew Charitable Trust (K.K.P.), The Miami Project to Cure Paralysis, and the Buoniconti Fund (K.K.P., V.P.L., and P.T.). Acknowledgments: We thank Pingping Jia at the University of Miami Viral Vector Core and Melissa Carballosa-Gautam at the Miami Project. Correspondence should be addressed to either of the following: Pantelis Tsoulfas at the above address, E-mail: ptsoulfa@med.miami.edu; or Kevin K. Park at the above address, E-mail: kpark@med.miami.edu. DOI:http://dx.doi.org/10.1523/ENEURO.0093-17.2017 Copyright {\textcopyright} 2017 Bray et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. Publisher Copyright: {\textcopyright} 2017 Bray et al.",
year = "2017",
month = jul,
day = "1",
doi = "10.1523/ENEURO.0093-17.2017",
language = "English",
volume = "4",
journal = "eNeuro",
issn = "2373-2822",
number = "4",
}