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Alon Kahana, Ryan M Kelly, Cuilee Sha, Phillip E Kish; Adult Abducens Nerve and Lateral Rectus Muscle Regenerate in a Coordinated Fashion Following Injury, Revealing Important Biological Interactions.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1147.
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© ARVO (1962-2015); The Authors (2016-present)
Ocular motility disorders represent common causes of visual dysfunction. Using a zebrafish model of lateral rectus (LR) injury and regeneration , we investigate the role of the regenerating abducens nerve.
Adult zebrafish LR muscle and abducens nerve were transected. IF for Gap43, tubulin, myosin, synaptotagmin, and fluorescent alpha-bungarotoxin were used to visualize muscle and nerve during regeneration. Vivo morpholino retrograde transport was used to knock down Gap43 expression in the motoneuron, and pharmacologic and genetic inhibition of growth factors and the proteasome were used to block muscle regeneration, as described [2,3].
Retrograde transport of injected vivo MO achieved efficient knockdown of gene expression, confirmed by IF revealing a decrease of >86% in Gap43 expression (by fluorescence intensity) in 85.7% of fish at 72 hpi (Figure). Blocking axon regeneration appeared to delay muscle regeneration. Pharmacologic and genetic inhibition of muscle regeneration had more limited but quantifiable impact on nerve regeneration. NMJ endplates were broadly preserved throughout the regeneration process, and abducens axon growth targeted residual NMJ endplates as well as forming new ones.
Muscle and nerve regeneration occur in a coordinated fashion, with substantial biological interactions throughout the process. We have developed a model in which the basic biology of nerve-muscle interactions following injury can be investigated in molecular detail.References:1. Saera-Vila, A., et al., Invest Ophthalmol Vis Sci, 2015. 56(8): p. 4977-93.2. Saera-Vila, A., et al., Autophagy, 2016: p. 1864-1875.3. Saera-Vila, A., P.E. Kish, and A. Kahana, Cell Signal, 2016. 28(9): p. 1196-204.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
Gap43 expression in MO injected vs control EOM. Gap 43 expression is reduced >86% in MO injected vs non-injected control nerve. A, B: Untreated control muscle 72 hours post injury (hpi), revealing muscle (DIC) and nerve (Gap43) regeneration. C, D: Following retrograde transport of vivo MOs, Gap43 expression is dramatically reduced (C) while muscle regeneration is altered (D).
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