title: Corneal endothelial integrity in mice lacking extracellular superoxide dismutase.
abstract: OBJECTIVE
  To evaluate corneal endothelial morphology in mice without secreted extracellular superoxide dismutase (SOD) in normal ageing and in a lipopolysaccharide (LPS)-induced inflammation model and to measure the contents of SOD isoenzymes in the mouse cornea and the superoxide radical concentrations in corneas with and without extracellular SOD.
  
  
  METHODS
  The central corneal endothelium of wild-type and extracellular SOD-null mice were studied in micrographs at eight different ages and after a unilateral intravitreal injection of LPS, with the contralateral eye serving as the control. The activities of the SOD isoenzymes in the mouse cornea were determined with a direct assay, the superoxide radical concentration was assessed by lucigenin-induced chemiluminescence, and the extracellular SOD distribution was mapped with immunohistochemistry.
  
  
  RESULTS
  The activities of the cytosolic Cu- and Zn-containing SOD, the mitochondrial Mn-containing SOD and extracellular SOD were 4300, 15, and 340 U/g wet weight, respectively. Extracellular SOD was found in the epithelium, stroma, and endothelium. The concentration of extracellular superoxide radicals was doubled in extracellular SOD-null corneas, and the endothelial cell density decreased more with age in extracellular SOD-null than in wild-type control corneas. In the LPS-induced inflammation model, the cell density decreased more, and the cells became more irregular in extracellular SOD-null than in wild-type corneas.
  
  
  CONCLUSIONS
  In the mouse cornea, absence of extracellular SOD leads to a higher concentration of extracellular superoxide radicals, an enhancement in the spontaneous age-related loss of endothelial cells, and an increased susceptibility to acute inflammatory endothelial damage. Extracellular SOD is likely to have a protective role in the corneal endothelium.
authors.affiliation: Department of Clinical Sciences/Ophthalmology, Division of Medical Biosciences, Umeå University Hospital, Sweden. anders_behndig@hotmail.com
authors.forename: A
authors.initials: A
authors.lastname: Behndig
authors.forename: K
authors.initials: K
authors.lastname: Karlsson
authors.forename: T
authors.initials: T
authors.lastname: Brännström
authors.forename: M L
authors.initials: ML
authors.lastname: Sentman
authors.forename: S L
authors.initials: SL
authors.lastname: Marklund
mesh_terms: D000166:Acridines / Q000378:metabolism; D000375:Aging / Q000473:pathology; D000818:Animals; D002452:Cell Count; D016923:Cell Death; D004728:Endothelium, Corneal / Q000201:enzymology* / Q000473:pathology; D005260:Female; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000502:physiology; D008070:Lipopolysaccharides; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D012475:Salmonella; D013482:Superoxide Dismutase / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology
chemical_list: D000166:Acridines; D007527:Isoenzymes; D008070:Lipopolysaccharides; D013481:Superoxides; C033472:10,10'-dimethyl-9,9'-biacridinium; D013482:Superoxide Dismutase