POSTNATAL RETINAL GANGLION-CELLS IN-VITRO - PROTECTION AGAINST REACTIVE OXYGEN SPECIES (ROS)-INDUCED AXONAL DEGENERATION BY COCULTURED ASTROCYTES

Citation
R. Lucius et J. Sievers, POSTNATAL RETINAL GANGLION-CELLS IN-VITRO - PROTECTION AGAINST REACTIVE OXYGEN SPECIES (ROS)-INDUCED AXONAL DEGENERATION BY COCULTURED ASTROCYTES, Brain research, 743(1-2), 1996, pp. 56-62
Citations number
48
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences
Journal title
Brain research → ACNP
ISSN journal
0006-8993
Volume
743
Issue
1-2
Year of publication
1996
Pages
56 - 62
Database
ISI
SICI code
0006-8993(1996)743:1-2<56:PRGI-P>2.0.ZU;2-J
Abstract
Reactive oxygen species (ROS) are supposed to be involved in neurodege nerative processes like Parkinson's or Alzheimer's disease. Beside thi s there are an increasing number of studies indicating an involvement of ROS in traumatic brain injury. We therefore studied the potential r ole of astrocytes against neurotoxic effects of ROS in cocultures of r at cortical astrocytes with regenerating postnatal retinal ganglion ce lls (RGC). The sydnonimine SIN-1, which spontaneously decomposes to yi eld nitric oxide (NO) and superoxide anion radicals, led to axonal deg eneration at concentrations between 1 mu M and 10 mu M. Comparable eff ects were seen after addition of iron salts (Fe2(+)/Fe3(+)), which cat alyze the generation of hydroxyl radicals. In contrast, in cocultures of RGC with astrocytes or after addition of free radical scavengers th ere was no neurotoxic/neurodegenerative effect of ROS as compared with control cultures. Vitamin E (1-10 mu M) and vitamin C (10-100 mu M) a bolished 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 p arameters were greatly enhanced. These results suggest that (i) astroc ytes are able to protect retinal ganglion cells against ROS-induced ox idative stress, (ii) astrocytes release soluble neurotrophic factors s upporting RGC axonal regeneration, and (iii) free radical production a fter tissue injury may partly contribute to the failure of axonal rege neration in the adult mammalian central nervous system.