Differential tumor necrosis factor expression by resident retinal cells from experimental uveitis-susceptible and...

Experimental autoimmune uveoretinitis (EAU) and endotoxin-induced uveitis (EIU), models for human ocular immunopathological syndromes, result in ocular inflammation in susceptible, but not in resistant rat strains. Moreover rapid photoreceptor degeneration occurs in susceptible rats developing EAU. In order to see whether differences in local ocular immune regulation may account for changes in resistance or susceptibility, we have examined the in vitro production of the cytotoxic cytokine tumor necrosis factor (TNF) by two resident ocular cell types, retinal Müller glia (RMG) and retinal pigmented epithelium (RPE). These cells were isolated and cultured in vitro from Lewis (Lew) (highly susceptible), Lew x Brown-Norway (BN) F1 hybrid (susceptible), BN and Long-Evans (LE) (resistant or poorly susceptible) rats. Constitutive production of the cytokine TNF, or its liberation in response to either interferon-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 RPE 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 20 pg/10(5) cells, respectively) and remained undetectable in LE RMG and 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 vitro conditions, which may play a key role in initiating or perpetuating local immune responses.