DECORIN AND BIGLYCAN OF NORMAL AND PATHOLOGICAL HUMAN CORNEAS

PURPOSE. Corneas with scars and certain chronic pathologic conditions contain highly sulfated dermatan sulfate, but little is known of the c ore proteins that carry these atypical glycosaminoglycans. In this stu dy the proteoglycan proteins attached to dermatan sulfate in normal an d pathologic human corneas were examined to identify primary genes inv olved in the pathobiology of corneal scarring. METHODS. Proteoglycans from human corneas with chronic edema, bullous keratopathy, and kerato conus and from normal corneas were analyzed using sodium dodecyl sulfa te-polyacrylamide gel electrophoresis (SDS-PAGE), quantitative immunob lotting, and immunohistology with peptide antibodies to decorin and bi glycan. RESULTS. Proteoglycans from pathologic corneas exhibit increas ed size heterogeneity and binding of the cationic dye alcian blue comp ared with those in normal corneas. Decorin and biglycan extracted from normal and diseased corneas exhibited similar molecular size distribu tion patterns. In approximately half of the pathologic corneas, the le vel of biglycan was elevated an average of seven times above normal, a nd decorin was elevated approximately three times above normal. The in creases were associated with highly charged molecular forms of decorin and biglycan, indicating modification of the proteins with dermatan s ulfate chains of increased sulfation. Immunostaining of corneal sectio ns showed an abnormal stromal localization of biglycan in pathologic c orneas. CONCLUSIONS. The increased dermatan sulfate associated with ch ronic corneal pathologic conditions results from stromal accumulation of decorin and particularly of biglycan in the affected corneas. These proteins bear dermatan sulfate chains with increased sulfation compar ed with normal stromal proteoglycans.