Macular corneal dystrophy. Studies of sulfated glycosaminoglycans in corneal explant and confluent stromal cell cultures.
The inherited disorder macular corneal dystrophy (MCD), a localized corneal mucopolysaccharidosis, is currently thought to result from an inability to catabolize corneal keratan sulfate (keratan sulfate 1). As studies on isolated cells have provided insight into metabolic abnormalities in other inherited disorders, we investigated cultured corneal fibroblasts from 4 patients with MCD from several standpoints. Lines of corneal fibroblasts with MCD could not be distinguished from controls with cytochemical methods known to stain the naturally occurring accumulations. In contrast to cultured fibroblasts from patients with mucopolysaccharidoses Type I-H (Hurler syndrome) and Type II (Hunter syndrome), corneal fibroblasts from patients with MCD did not accumulate abnormal quantities of (35)S-sulfate-labeled glycosaminoglycans, but like normal corneal and cutaneous fibroblasts reached a state of equilibrium within 2 days. Also, the rate at which sulfated glycosaminoglycans were removed from cultured corneal fibroblasts in MCD by secretion and degradation more closely resembled that of normal cells than those with the systemic mucopolysaccharidoses. The secretion of sulfated glycosaminoglycans into the nutrient medium by corneal fibroblasts from patients with MCD occurred at a linear rate comparable to that of other cells studied. The aforementioned data, nonetheless, remain consistent with the hypothesis that MCD is an inherited disorder of keratan sulfate I (corneal keratan sulfate) catabolism, as isolated corneal fibroblasts in contrast to corneal explants synthesize little or no keratan sulfate in culture. In view of the latter, we also compared the profile of (35)S-labeled glycosaminoglycans produced by a corneal explant from a patient with MCD with that normally synthesized by human corneal explants. The latter synthesized and secreted a population of (35)S-sulfate-labeled glycosaminoglycans with properties of keratan sulfate. Considerably less material with these attributes was identified with the same analytic techniques in the cornea with MCD or in its surrounding medium after the abnormal cornea had been incubated under identical conditions. In addition to manifesting an impaired synthesis of corneal keratan sulfate-like material, the cornea with MCD produced a greater percentage of chondroitin-6-sulfate than normal. These findings suggest that the synthesis of corneal keratan sulfate and other glycosaminoglycans may be altered in MCD.
D000328:Adult; D002478:Cells, Cultured; D003317:Corneal Dystrophies, Hereditary / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007632:Keratan Sulfate / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009083:Mucopolysaccharidoses / Q000378:metabolism
D006025:Glycosaminoglycans; D007632:Keratan Sulfate