Tumor necrosis factor and nitric oxide production by retinal Müller glial cells from rats exhibiting inherited retinal dystrophy.
The primary cause of the inherited retinal dystrophy observed in Royal College of Surgeons (RCS) rats is located in the retinal pigmented epithelium, which is unable to phagocytize photoreceptor outer segments. We have demonstrated here that retinal Müller glial (RMG) cells obtained from RCS dystrophic rats and stimulated in vitro with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) accumulated higher levels of tumor necrosis factor (TNF) and inducible nitric oxide synthase (NOS II) mRNA and released in culture supernatants significantly higher amounts of TNF and nitrite compared to cells derived from nondystrophic controls. The TNF and NOS II mRNA expression and TNF and nitrite synthesis induced in RMG cells from both strains by LPS + IFN-gamma was significantly prevented by including transforming growth factor-beta (TGF-beta) in the culture medium. Coincubation of the stimulants with an inhibitor of NOS II, NG-monomethyl-L-arginine (L-NMMA), while inhibiting nitrite synthesis, induced an increase of TNF production in supernatants from RMG cells without increasing TNF mRNA levels. The retinal dystrophy observed in RCS dystrophic rats could result from an abnormal susceptibility of RMG cells form RCS dystrophic rats to produce TNF and NO in response to stimulants. Administration of the immunomodulatory cytokine TGF-beta or inhibitors of NOS II would provide additional research avenues for photoreceptor rescue.
Cotinet
A
A
Laboratoire d'Immunopathologie de l'Oeil, INSERM U86, Paris, France.
Goureau
O
O
Hicks
D
D
Thillaye-Goldenberg
B
B
de Kozak
Y
Y
D000818:Animals; D004790:Enzyme Induction; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011922:Rats, Mutant Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase