DIFFERENTIAL TUMOR-NECROSIS-FACTOR AND NITRIC-OXIDE PRODUCTION IN RETINAL MULLER GLIAL-CELLS FROM C3H HEN AND C3H/HEJ MICE/

Tumor necrosis factor (TNF) and nitric oxide (NO) have been shown to p lay a role in the pathogenesis of endotoxin-induced uveitis (EIU) in r ats. Susceptibility to develop EIU in vivo is con-elated with the exte nt of TNF production by retinal Muller glial cells (RMG). Moreover, RM G cells from the susceptible Lewis rat strain synthesize high amounts of nitrite under in vitro stimulation. Variations in susceptibility to endotoxin are observed among mice strains: C3H/HeN mice are known to be susceptible to develop EIU while C3H/HeN are refractory. We show he re that treatment of RMG cells from both strains with LPS + IFN-gamma does not induce TNF synthesis in culture supernatants but produces hig h amounts of NO only in the supernatants from activated C3H/HeN RMG ce lls. The addition of TNF in the culture medium containing LPS/IFN-gamm a further increases nitrite production in C3H/HeN RMG cells and allows the synthesis of low levels of nitrite in C3H/HeJ RMG cells. Addition of a specific NO synthase inhibitor, N-G-monomethyl-L-arginine (L-NMM A), blocks NO release. We have previously shown that intraperitoneal i njections of the NO synthase inhibitor, N-G-nitro-L-arginine methyl es ter (L-NAME) which inhibited nitrite and TNF release in the ocular med ia reduced EIU in rat. We conclude here that the in vivo susceptibilit y to develop EIU in mice is correlated with the extent of in vitro nit rite production by RMG cells confirming the implication of NO in the i nduction of ocular inflammation. The low level of retinal inflammation observed during EIU in C3H/HeN mice compared to rats could be related to the absence of TNF production by RMG cells.