Axonal Regeneration of Fish Optic Nerve after Injury

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  • Matsukawa Toru
    Department of Molecular Neurobiology, Graduate School of Medicine, Kanazawa University Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency
  • Arai Kunizo
    Department of Molecular Neurobiology, Graduate School of Medicine, Kanazawa University Laboratory of Molecular and Cellular Physiology, Faculty of Pharmaceutical Sciences, Kanazawa University Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency
  • Koriyama Yoshiki
    Department of Molecular Neurobiology, Graduate School of Medicine, Kanazawa University Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency
  • Liu Zhongwu
    Department of Molecular Neurobiology, Graduate School of Medicine, Kanazawa University
  • Kato Satoru
    Department of Molecular Neurobiology, Graduate School of Medicine, Kanazawa University Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency

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Since Sperry's work in the 1950s, it has been known that the central nervous system (CNS) neurons of lower vertebrates such as fish and amphibians can regenerate after axotomy, whereas the CNS neurons of mammals become apoptotic after axotomy. The goldfish optic nerve (ON) is one of the most studied animal models of CNS regeneration. Morphological changes in the goldfish retina and tectum after ON transection were first researched in the 1970s—1980s. Many biochemical studies of neurite outgrowth-promoting substances were then carried out in the 1980s—1990s. Many factors have been reported to be active substances that show increased levels during fish ON regeneration, as shown by using various protein chemistry techniques. However, there are very few molecular cloning techniques for studying ON regeneration after injury. In this review article, we summarize the neurite outgrowth-promoting factors reported by other researchers and describe our strategies for searching for ON regenerating molecules using a differential hybridization technique in the goldfish visual system. The process of goldfish ON regeneration after injury is very long. It takes about half a year from the start of axonal regrowth to complete restoration of vision. The process has been classified into three stages: early, middle and late. We screened for genes with increased expression during regeneration using axotomized goldfish retinal and tectal cDNA libraries and obtained stage-specific cDNA clones that were upregulated in the retina and tectum. We further discuss functional roles of these molecules in the regeneration processes of goldfish ON.

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