Osteopontin is proinflammatory in experimental autoimmune uveitis.
OBJECTIVE
Osteopontin (OPN) has been implicated in inflammatory and wound-healing processes. Increased OPN mRNA levels have been reported in experimental autoimmune uveitis (EAU), but the function of OPN in the inflamed eye is unknown. The purpose of this study was to investigate the role of OPN in the pathogenesis of EAU.


METHODS
EAU was induced in OPN-null and wild-type (WT) mice by immunization with interphotoreceptor retinoid-binding protein (IRBP). Immunofluorescence experiments were performed to identify OPN-positive cells in WT mice. Disease incidence, serum IRBP antibody levels, vitreous infiltrates, retinal granulomas, and lymphocyte proliferation were assessed in OPN-null and WT mice. To determine whether OPN could induce an EAU-like condition, purified OPN and OPN fragments were injected intraocularly into WT mice and vitreous infiltrates were characterized and quantified.


RESULTS
In WT EAU-positive eyes, cell types with increased OPN immunoreactivity were identified as F4/80-positive macrophages/microglia and CD4-positive T cells. OPN-null mice manifested attenuated disease with decreased vitreous infiltrates, fewer granulomas, less lymphocyte proliferation, and lower serum IRBP antibody levels. Exogenous full-length OPN, as well as N- and C-terminal fragments, induced leukocyte infiltration and retinal folding, with some similarities to EAU.


CONCLUSIONS
The results demonstrate that OPN is proinflammatory in EAU and may be important for recruitment and activation of leukocytes in retinal inflammation.
Hikita
Sherry T
ST
Neuroscience Research Institute and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara (UCSB), California 93106-5060, USA.
Vistica
Barbara P
BP
Jones
Heather R
HR
Keswani
Jennifer R
JR
Watson
Morgan M
MM
Ericson
Vivian R
VR
Ayoub
George S
GS
Gery
Igal
I
Clegg
Dennis O
DO
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000276:immunology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D007267:Injections; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D018613:Microscopy, Confocal; D053495:Osteopontin; D012177:Retinol-Binding Proteins / Q000276:immunology; D012795:Sialoglycoproteins / Q000494:pharmacology / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology; D015866:Uveitis, Posterior / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D014822:Vitreous Body; D000099214:Retinol-Binding Proteins, Interstitial
D001323:Autoantibodies; D005136:Eye Proteins; D053495:Osteopontin; D012177:Retinol-Binding Proteins; D012795:Sialoglycoproteins; D000099214:Retinol-Binding Proteins, Interstitial; C506896:Spp1 protein, mouse