27The present study is designed to identify the influences of genetic background to optic nerve 28 regeneration using the two parental strains C57BL/6J and DBA/2J and 7 BXD recombinant 29 inbred strains. To study regeneration in the optic nerve, Pten was knocked down in the retinal 30 ganglion cells using AAV, and a mild inflammatory response was induced by an intravitreal 31 injection of zymosan with CPT-cAMP, and the axons were damaged by optic nerve crush (ONC). 32Regenerating axons were labeled by Cholera Toxin B and quantified 14 days after ONC. The 33 number of axons at 0.5 mm and 1 mm from the crush site were counted. In addition, we 34 measured the distance that 5 axons had grown down the nerve and the longest distance a single 35 axon reached. Results showed a considerable amount of differential axonal growth across all 9 36 BXD strains. There was a significant difference (P=0.014 Mann-Whitney U test) in the 37 regenerative capacity in the number of axons reaching 0.5 mm from a low of 1487.6 ± 264.9 38 axons in BXD102 to a high of 4175.8 ± 648.6 axons in BXD29. There were also significant 39 differences (P=0.014 Mann-Whitney U test) in the distance axons traveled, looking at a 40 minimum of 5 axons with the shortest distance was 787.2 ± 46.5µm in BXD102 to a maximum 41 distance of 2025.5 ± 223.3µm in BXD29. These results reveal that genetic background can 42 modulate axonal regeneration and that the BXD strains are a particularly well-suited model 43 system. 44 45 peer-reviewed)
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