DIFFERENTIAL TUMOR-NECROSIS-FACTOR EXPRESSION BY RESIDENT RETINAL CELLS FROM EXPERIMENTAL UVEITIS-SUSCEPTIBLE AND UVEITIS-RESISTANT RAT STRAINS

Experimental autoimmune uveoretinitis (EAU) and endotoxin-induced uvei tis (EIU), models for human ocular immunopathological syndromes, resul t in ocular inflammation in susceptible, but not in resistant rat stra ins. Moreover rapid photoreceptor degeneration occurs in susceptible r ats developing EAU. In order to see whether differences in local ocula r immune regulation may account for changes in resistance or susceptib ility, we have examined the in vitro production of the cytotoxic cytok ine tumor necrosis factor (TNF) by two resident ocular cell types, ret inal Muller glia (RMG) and retinal pigmented epithelium (RPE). These c ells were isolated and cultured in vitro from Lewis (Lew) (highly susc eptible), Lew X Brown-Norway (BN) F1 hybrid (susceptible), BN and Long -Evans (LE) (resistant or poorly susceptible) rats. Constitutive produ ction of the cytokine TNF, or its liberation in response to either int erferon-gamma (IFN-gamma) or lipopolysaccharide (LPS) alone, was very low in RMG and RPE cells, irrespective of the strain. It was strongly induced by combined treatment with IFN-gamma and LPS in Lew RMG and RP E cells (mean values of 140 and 150 pg/10(5) cells, respectively) and in Lew X BN F1 RMG and RPE cells (mean values of 125 and 190 pg/10(5) cells, respectively), much less so from BN RMG and RPE cells (30 and 2 0 pg/10(5) cells, respectively) and remained undetectable in LE RMG an d RPE cells. Hence susceptibility to EAU and EIU in vivo is correlated with the extent of TNF production by these two cell. types under in v itro conditions, which may play a key role in initiating or perpetuati ng local immune responses.