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Jiaxing Wang, Ying Li, Rebecca King, Felix Struebing, Eldon Geisert; Genomic modulation of optic nerve regeneration in mice. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5155.
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© ARVO (1962-2015); The Authors (2016-present)
The present study is designed to identify the influences of genetic background on optic nerve regeneration using the two parental strains C57BL/6J and DBA/2J and 13 BXD recombinant inbred strains.
To study regeneration in the optic nerve, Pten was knocked down in the retinal ganglion cells using AAV delivery of shRNA, and the induction of a mild inflammatory response by an intravitreal injection of zymosan with CPT-cAMP. The axons of the retinal ganglion cells were damaged by optic nerve crush (ONC). Following a 12-day survival period, regenerating axons were labeled by Cholera Toxin B and two days later the regenerating axons within the optic nerve were examined. The number of axons at 0.5 mm and 1 mm from the crush site were counted. In addition, we measured the distance that 5 axons had grown down the nerve and the longest distance a single axon reached. The data are presented as a mean and standard error of the mean. The Mann-Whitney U test was used to determine statistical significance.
The analysis revealed a considerable amount of differential axonal regeneration across all 15 strains. There was a significant difference (p<0.005) in the regenerative capacity in the number of axons counted at 0.5 mm and axons counted at 1mm from the crush site. At 1 mm from the crush site, the strain with the fewest axons was BXD51 (0.5 ± 0.3 axons) and the strain with the most abundant regeneration was observed in the BXD90 (19.1 ± 2.3 axons). There were also significant differences (P<0.01) in the distance axons traveled. If we look at the distance 5 axons traveled, the strain with the shortest distance was BXD102 (787.2 ± 46.5µm). The strain with the longest distance was BXD29 (2025.5 ± 223.3µm). In all measures of axonal growth, the parental strains (C57BL/6J and DBA/2J) were not the extremes, demonstrating genetic transgression.
Genetic background has a profound effect on axonal regeneration. Selected BXD strains have a 19-fold variation in the number of regenerating axons at 1mm from the crush site. There is also a 3-fold difference in distance regenerating axons traveled in the damaged optic nerve. Our data reveal that genomic elements are modulating the induced optic nerve regeneration. Furthermore, based on the genetic transgression of our current data, there are at least two genomic loci responsible for the difference in regenerative capacity observed in the BXD strains.
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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