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Requirement for Nitric Oxide in Retinal Neuronal Cell Death Induced by Activated Müller Glial Cells
Author(s) -
Goureau O.,
RégnierRicard F.,
Courtois Y.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0722506.x
Subject(s) - programmed cell death , peroxynitrite , retinal , microbiology and biotechnology , nitric oxide synthase , retina , muller glia , nitric oxide , biology , neurotoxicity , apoptosis , chemistry , biochemistry , superoxide , endocrinology , neuroscience , stem cell , toxicity , progenitor cell , organic chemistry , enzyme
Retinal Müller glial cells express the inducible isoform (‐2) of nitric oxide (NO) synthase (NOS) in vitro after stimulation by lipopolysaccharide (LPS) and interferon‐γ (IFN‐γ) or in vivo in some retinal pathologies. Because NO may have beneficial or detrimental effects in the retina, we have used cocultures of retinal neurons with retinal Müller glial (RMG) cells from mice disrupted for the gene of NOS‐2 [NOS‐2 (‐/‐)] to clarify the role of NO in retinal neurotoxicity. We first demonstrated that NO produced by activated RMG cells was not toxic for RMG cells themselves. Second, the NO released from LPS/IFN‐γ‐stimulated RMG cells induced neuronal cell death, because no neuronal cell death has been observed in cocultures with RMG cells from NOS‐2 (‐/‐) mice and because inhibition of NOS‐2 induction by transforming growth factor‐β or blockade of NO release by different NOS inhibitors prevented neuronal cell death. Addition of urate, a peroxynitrite scavenger, or superoxide dismutase partially prevented neuronal cell death induced by NO, whereas the presence of a poly(ADP‐ribose) synthetase inhibitor, caspase inhibitors, or a guanylate cyclase inhibitor had no significant effect on cell death. These results demonstrated that a large release of NO from RMG cells in responsible for retinal neuronal cell death in vitro, suggesting a neurotoxic role for NO and peroxynitrite during retinal inflammatory or degenerative diseases, where RMG cells were activated.