Endotoxin-induced uveitis in cyclooxygenase-2-deficient mice

Invest Ophthalmol Vis Sci. 2004 Jul;45(7):2306-13. doi: 10.1167/iovs.03-0756.


Purpose: Endotoxin-induced uveitis (EIU) is a model that mimics human acute anterior uveitis. Cyclooxygenase (COX)-2 is an enzyme that initiates the conversion of arachidonic acid (AA) into prostaglandins (PGs), whereas 5-lipoxygenase (5-LO) generates leukotrienes (LT). The purpose of this study was to delineate the role of COX-2 in acute ocular inflammation.

Methods: EIU was induced in wild-type (WT), heterozygotic (COX-2(+/-)) and COX-2 null (COX-2(-/-)) mice by injection of lipopolysaccharide (LPS). Other mice were coinjected with LPS and IFN gamma. Ocular histology, serum cytokines, and AA products determined by ELISA, and relevant ocular messengers determined by RT-PCR were compared among the different groups.

Results: Histology showed that the EIU score was significantly enhanced in COX-2(-/-) mice in comparison to WT and COX-2(+/-). PGE(2) was increased in WT and COX-2(+/-) EIU but not in COX-2(-/-) EIU. LTB(4) in serum and ocular 5-LO transcripts were increased in COX-2(-/-) EIU mice in comparison with WT and COX-2(+/-) EIU mice. IL-6 increased, whereas IFN gamma decreased both in serum and ocular transcripts in COX-2(-/-) EIU mice in comparison with WT and COX-2(+/-). Furthermore, EIU was suppressed in mice treated with recombinant IFN gamma, as shown by the decreased EIU scores, the presence of serum LTB(4) and IL-6 and ocular 5-LO and IL-6 mRNA, and the increases in serum IFN gamma and ocular IFN gamma, particularly in COX-2(-/-) mice.

Conclusions: These data suggest that disturbance of the AA pathway exacerbates EIU in COX-2-deficient mice. IFN gamma moderately reverses this exacerbation and protects against EIU.

MeSH terms

  • Animals
  • Arachidonate 5-Lipoxygenase / genetics
  • Arachidonic Acid / metabolism
  • Cyclooxygenase 2
  • Dinoprostone / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interferon-gamma / pharmacology
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Isoenzymes / deficiency*
  • Isoenzymes / genetics
  • Leukotriene B4 / blood
  • Lipopolysaccharides / toxicity*
  • Mice
  • Mice, Knockout
  • Prostaglandin-Endoperoxide Synthases / deficiency*
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Recombinant Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Salmonella typhimurium*
  • Uveitis, Anterior / chemically induced*
  • Uveitis, Anterior / enzymology*
  • Uveitis, Anterior / pathology
  • Uveitis, Anterior / prevention & control


  • Interleukin-6
  • Isoenzymes
  • Lipopolysaccharides
  • Recombinant Proteins
  • Leukotriene B4
  • Arachidonic Acid
  • Interferon-gamma
  • Arachidonate 5-Lipoxygenase
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone