title: Sema-3A indirectly disrupts the regeneration process of goldfish optic nerve after controlled injury.
abstract: BACKGROUND
  Neurons of adult mammalian CNS are prevented from regenerating injured axons due to formation of a non-permissive environment. The retinal ganglion cells (RGC), which are part of the CNS, share this characteristic. In sharp contrast, the RGC of lower vertebrates, such as fish, are capable of re-growing injured optic nerve axons, and achieve, through a complex multi-factorial process, functional vision after injury. Semaphorin-3A (sema-3A), a member of the class 3 semaphorins known for its repellent and apoptotic activities, has previously been shown to play a key role in the formation of a non-permissive environment after CNS injury in mammalians.
  
  
  METHODS
  The expression of sema-3A and its effect on regenerative processes in injured gold fish retina and optic nerve were investigated in this study. Unilateral optic nerve axotomy or crush was induced in goldfish. 2 microl sema-3A was injected intraviterally 48 hours post injury. Neuronal viability was measured using the lipophilic neurotracer dye 4-Di-10-Asp. Axonal regeneration was initiated using the anterograde dye dextran. Retinas and optic nerves were collected at intervals of 2, 3, 7, 14 and 28 days after the procedure. Using Western blot and immunohistochemical analysis, the expression levels of semaphorin-3A, axonal regeneration, the removal of myelin debris and macrophage invasion were studied.
  
  
  RESULTS
  We found a decrease in sema-3A levels in the retina at an early stage after optic nerve injury, but no change in sema-3A levels in the injured optic nerve. Intravitreal injection of sema-3A to goldfish eye, shortly after optic nerve injury, led to destructive effects on several pathways of the regenerative processes, including the survival of retinal ganglion cells, axonal growth, and clearance of myelin debris from the lesion site by macrophages.
  
  
  CONCLUSIONS
  Exogenous administration of sema-3A in fish indirectly interferes with the regeneration process of the optic nerve. The findings corroborate our previous findings in mammals, and further validate sema-3A as a key factor in the generation of a non-permissive environment after transection of the optic nerve.
authors.affiliation: Departments of Neurobiology, George S. Wise, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, 69978, Israel.
authors.forename: Shira
authors.initials: S
authors.lastname: Rosenzweig
authors.forename: Dorit
authors.initials: D
authors.lastname: Raz-Prag
authors.forename: Anat
authors.initials: A
authors.lastname: Nitzan
authors.forename: Ronit
authors.initials: R
authors.lastname: Galron
authors.forename: Ma'ayan
authors.initials: M
authors.lastname: Paz
authors.forename: Gunnar
authors.initials: G
authors.lastname: Jeserich
authors.forename: Gera
authors.initials: G
authors.lastname: Neufeld
authors.forename: Ari
authors.initials: A
authors.lastname: Barzilai
authors.forename: Arieh S
authors.initials: AS
authors.lastname: Solomon
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D019771:Axotomy; D015153:Blotting, Western; D002452:Cell Count; D002470:Cell Survival; D019084:Fluorescent Antibody Technique, Indirect; D006054:Goldfish; D007267:Injections; D008264:Macrophages / Q000502:physiology; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D009900:Optic Nerve / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D040121:Semaphorin-3A / Q000494:pharmacology / Q000502:physiology*; D014822:Vitreous Body
chemical_list: D040121:Semaphorin-3A
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