Aims-To examine the hypothesis that apoptosis of infiltrating cells contrib
utes to spontaneous resolution of uveitis in clinically relevant rodent mod
els.
Methods-Experimental melanin induced uveitis (EMIU) was induced in Fischer
344 rats by immunisation with 250 mu g bovine ocular melanin. Endotoxin ind
uced uveitis (EIU) was induced by injection of 200 mu g Escherichia coli li
popolysaccharide. Formalin fixed, paraffin embedded ocular cross sections w
ere stained by terminal deoxynucleotidyl transferase mediated deoxyuridine
triphosphate biotin nick end labelling (TUNEL) to identify apoptotic cells.
Indirect immunoperoxidase staining of paraformaldehyde lysine periodate fi
xed tissue cross sections was used to demonstrate expression of inducible n
itric oxide synthase (iNOS).
Results-TUNEL positive mononuclear cells were observed in the anterior uvea
during both EMIU and EIU at all selected time points. However, whereas the
majority of mononuclear cells appeared apoptotic from the outset of diseas
e, neutrophils were notably TUNEL negative at all time points examined. Man
y infiltrating neutrophils expressed iNOS.
Conclusion-Apoptosis occurs early in the course of rat EMIU and EIU, and ma
y contribute to resolution of these diseases. In general, infiltrating mono
nuclear cells die rapidly, while neutrophils survive, producing inducible n
itric oxide synthase which may contribute to disease pathogenesis.