Peptide growth factors but not ganglioside protect against excitotoxicity in rat retinal neurons in vitro.
Glutamate is the major excitatory neurotransmitter in the retina, but excessive stimulation of its receptors leads to widespread neuronal stress and death. Both growth factors and gangliosides display important influences on responses to neuronal injury and degeneration. In this study, we have investigated the potential protective effects of two well characterized growth factors, epidermal and basic fibroblast growth factor (EGF and bFGF respectively), and the monosialoganglioside GM1, on cultured rat retinal neurons submitted to toxic levels of excitatory amino acids. Application of 1 mM glutamic acid reduced global neuronal viability by 80% when compared to control untreated cultures, whereas treatment with the glutamic acid agonist kainic acid (1 mM) led to specific, large decreases (75% reduction) in amacrine cell numbers. 24 h pretreatment with either EGF or bFGF (500 pM each) prevented the majority of excitatory amino acid-induced neuronal death, whereas similar treatment with 10(-5) M GM1 did not block neuronal degeneration. These findings demonstrate that EGF and bFGF act as neuroprotective agents against retinal excitotoxicity in vitro, whereas ganglioside GM1 is not effective in this particular paradigm.
Heidinger
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Laboratoire de Physiopathologie rétinienne, INSERM CJF 92 / 02, Médicale A, Centre Hospitalier et Universitaire de Strasbourg, France. heidinger@neurochem.u-strasbg.fr
Hicks
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D
Sahel
J
J
Dreyfus
H
H
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000037:antagonists & inhibitors / Q000633:toxicity; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D010786:Photoreceptor Cells / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000166:cytology / Q000187:drug effects*
D018846:Excitatory Amino Acids; D006133:Growth Substances; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016222:Fibroblast Growth Factor 2; D005677:G(M1) Ganglioside; D004815:Epidermal Growth Factor; D007608:Kainic Acid