Endotoxin-induced uveitis in the rat: observations on altered vascular permeability, clinical findings, and histology.
A single intraperitoneal dose of endotoxin (lipopolysaccharide or LPS) induces an acute inflammatory response in the uveal tract of rats. This inflammation is characterized by a breakdown of the blood/aqueous barrier within 3 hr after the LPS and the subsequent development of clinical disease and a cellular infiltrate. Early change in vascular permeability, clinical, and pathological changes were dose dependent with the two highest doses (100 micrograms or 500 micrograms) producing more severe pathology. Clinical and histopathologic abnormalities peaked at 24 hr and were resolving by 48 hr. Although clinical and histologic changes correlated well, the degree of breakdown of the blood/aqueous barrier at 3 hr failed to predict the extent of the cellular exudate measured by either clinical or histologic criteria. In addition, pharmacologic suppression of the early vascular permeability changes with indomethacin, cyproheptadine, or both agents failed to protect the animals consistently from subsequently developing significant clinical disease or cellular infiltrates on histopathology. LPS-induced uveitis in the rat provides a simple, reproducible model for ocular inflammation without requiring direct eye manipulation. The mediators responsible for the early vascular permeability in this model appear to be distinct from the mediators primarily responsible for the subsequent cellular exudate.
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D003533:Cyproheptadine / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014602:Uvea / Q000187:drug effects / Q000473:pathology; D014605:Uveitis / Q000139:chemically induced* / Q000473:pathology
D004731:Endotoxins; D008070:Lipopolysaccharides; D003533:Cyproheptadine; D007213:Indomethacin