Superoxide dismutase isoenzymes in the normal and diseased human cornea.
OBJECTIVE
The human cornea, a tissue much exposed to oxidative stress, is rich in extracellular superoxide dismutase (SOD). In this study, the contents and distributions of the SOD isoenzymes in the normal human cornea were compared with those in corneas affected by keratoconus and bullous keratopathy.


METHODS
The central and peripheral parts of normal human corneas were analyzed separately. Central corneal buttons were obtained from patients with keratoconus and bullous keratopathy who were undergoing primary keratoplasty or retransplantation. SOD enzymatic activities were determined by a direct spectrophotometric method, and extracellular SOD and the cytosolic Cu- and Zn-containing SOD (CuZn-SOD) proteins were determined with ELISA and studied with immunohistochemistry.


RESULTS
The total SOD content, and particularly the extracellular SOD content, was lower in the central than in the peripheral normal cornea. CuZn-SOD and extracellular SOD were demonstrated in all three corneal layers. CuZn-SOD was found in cells, whereas extracellular SOD appeared to be localized on cell surfaces, in basal membranes, and in the stroma. In keratoconus, corneal levels of extracellular SOD were half those in the control corneas, whereas CuZn-SOD and the mitochondrial Mn-containing SOD levels were normal. In bullous keratopathy, apart from edematous dilution, SOD isoenzyme levels were essentially normal. In a remarkable finding, the same pattern in SOD isoenzyme levels as in the original disease was also found at retransplantation.


CONCLUSIONS
Extracellular SOD and CuZn-SOD show markedly different distribution patterns within the human cornea. Extracellular SOD activity in the central cornea is halved in keratoconus, compared with that in normal control corneas. The finding of a similar reduction at retransplantation in keratoconus suggests reduced corneal extracellular SOD synthesis in cells of the host as a cause of the low enzyme levels.
Behndig
A
A
Department of Clinical Sciences/Ophthalmology, Umeå University Hospital, Sweden. anders_behndig@hotmail.com
Karlsson
K
K
Johansson
B O
BO
Brännström
T
T
Marklund
S L
SL
D003315:Cornea / Q000201:enzymology*; D003316:Corneal Diseases / Q000201:enzymology* / Q000601:surgery; D016039:Corneal Transplantation; D004247:DNA / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007124:Immunoenzyme Techniques; D007527:Isoenzymes / Q000378:metabolism; D012086:Reoperation; D013482:Superoxide Dismutase / Q000378:metabolism*
D007527:Isoenzymes; D004247:DNA; D013482:Superoxide Dismutase