An optimal redox status for the survival of axotomized ganglion cells in the developing retina

The neuronal redox status influences the expression of genes involved in ne uronal survival. We previously showed that antioxidants may reduce the numb er of dying ganglion cells following axotomy in chick embryos. in the prese nt study, we show that various antioxidants, including the new spin trap az ulenyl nitrone and 1,3-dimethyl-2-thiourea, protect axotomized ganglion cel ls, confirming that neuronal death involves an imbalance of the cellular re dox status towards oxidation. However, high concentrations of antioxidants did not protect ganglion cells, suggesting that excessive reduction is detr imental for neurons. Simultaneous injections of two different antioxidants gave results only partly supporting this view. Combinations of azulenyl nit rone and N-acetyl cysteine in fact gave greater protection than either anti oxidant alone, whereas N-acetyl cysteine lost its neuroprotective effects a nd diminished those of alpha-phenyl-N-tert-butyl nitrone when the two compo unds were injected simultaneously. The results of the combined treatments s uggest that azulenyl nitrone and alpha-phenyl-N-tert-butyl nitrone do not h ave the same chemical effects within the ganglion cells. Moreover, N-acetyl cysteine's own antioxidant properties enhance the spin trapping effects of azulenyl nitrone but potentiate the toxicity of alpha-phenyl-N-tert-butyl nitrone. Our main conclusion is that neuronal survival requires the maintenance of t he redox status near an optimal set-point. "Reductive stress" may be as dan gerous as oxidative stress. (C) 1999 IBRO. Published by Elsevier Science Lt d.