Br J Ophthalmol 2000;84:205-211
( February )
Apoptosis is a prominent feature of acute anterior uveitis in the
Fischer 344 rat
J R Smitha, P H Hartb, S D Standfielda, D J Costera, S J Wingc, K A Williamsa
a Department
of Ophthalmology, Flinders University of South Australia, Adelaide,
Australia, b Department of Microbiology
and Infectious Diseases, c Arthritis Research Laboratory, University of
Adelaide, Adelaide, Australia
Correspondence to: Dr K A Williams, Department of Ophthalmology, Flinders
Medical Centre, Bedford Park, South Australia 5042, Australia
Accepted for publication 15 September 1999
AIMS To examine the
hypothesis that apoptosis of infiltrating cells contributes to
spontaneous resolution of uveitis in clinically relevant rodent models.
METHODSExperimental
melanin induced uveitis (EMIU) was induced in Fischer 344 rats by
immunisation with 250 µg bovine ocular melanin. Endotoxin induced
uveitis (EIU) was induced by injection of 200 µg
Escherichia coli lipopolysaccharide.
Formalin fixed, paraffin embedded ocular cross sections were stained by
terminal deoxynucleotidyl transferase mediated deoxyuridine
triphosphate biotin nick end labelling (TUNEL) to identify apoptotic
cells. Indirect immunoperoxidase staining of paraformaldehyde lysine
periodate fixed tissue cross sections was used to demonstrate
expression of inducible nitric oxide synthase (iNOS).
RESULTSTUNEL 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 disease,
neutrophils were notably TUNEL negative at all time points examined.
Many infiltrating neutrophils expressed iNOS.
CONCLUSIONApoptosis
occurs early in the course of rat EMIU and EIU, and may contribute to
resolution of these diseases. In general, infiltrating mononuclear
cells die rapidly, while neutrophils survive, producing inducible
nitric oxide synthase which may contribute to disease pathogenesis.
© 2000 by British Journal of Ophthalmology
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