title: Postnatal retinal ganglion cells in vitro: protection against reactive oxygen species (ROS)-induced axonal degeneration by cocultured astrocytes.
abstract: Reactive oxygen species (ROS) are supposed to be involved in neurodegenerative processes like Parkinson's or Alzheimer's disease. Beside this there are an increasing number of studies indicating an involvement of ROS in traumatic brain injury. We therefore studied the potential role of astrocytes against neurotoxic effects of ROS in cocultures of rat cortical astrocytes with regenerating postnatal retinal ganglion cells (RGC). The sydnonimine SIN-1, which spontaneously decomposes to yield nitric oxide (NO) and superoxide anion radicals, led to axonal degeneration at concentrations between 1 microM and 10 microM. Comparable effects were seen after addition of iron salts (Fe2+/Fe3+), which catalyze the generation of hydroxyl radicals. In contrast, in cocultures of RGC with astrocytes or after addition of free radical scavengers there was no neurotoxic/neurodegenerative effect of ROS as compared with control cultures. Vitamin E (1-10 microM) and vitamin C (10-100 microM) abolished the neurotoxic effect of both SIN-1 or iron ions. Beside this, there was an additional effect concerning the number and the length of neurites growing out from the retinal explant: in cocultures both parameters were greatly enhanced. These results suggest that (i) astrocytes are able to protect retinal ganglion cells against ROS-induced oxidative stress, (ii) astrocytes release soluble neurotrophic factors supporting RGC axonal regeneration, and (iii) free radical production after tissue injury may partly contribute to the failure of axonal regeneration in the adult mammalian central nervous system.
authors.affiliation: Anatomisches Institut, Universität Kiel, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Lucius
authors.forename: J
authors.initials: J
authors.lastname: Sievers
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology*; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D018920:Coculture Techniques; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007501:Iron / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009410:Nerve Degeneration / Q000187:drug effects / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000502:physiology*; D012016:Reference Values; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology*; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D014810:Vitamin E; C002385:linsidomine; D008981:Molsidomine; D007501:Iron; D001205:Ascorbic Acid