ABNORMALITIES OF PROTEOGLYCANS AND GLYCOPROTEINS SYNTHESIZED BY CORNEAL ORGAN-CULTURES DERIVED FROM PATIENTS WITH MACULAR CORNEAL-DYSTROPHY

  • 1 January 1983
    • journal article
    • research article
    • Vol. 48  (5) , 603-612
Abstract
Macular corneal dystrophy was previously suspected to be a localized storage disease of glycosaminoglycans; the nature of the storage product and the basic defect remain to be established. To learn more about this disease, the proteoglycans and glycoproteins synthesized by corneal organ cultures from 5 patients with macular corneal dystrophy and 6 individuals with surgically enucleated eyes and normal corneas were analyzed. This was done after incubating the corneas in Eagle''s minimal essential medium supplemented by fetal or newborn bovine serum and 3H-glucosamine and 35S-sulfate for 24 h and then extracting the tissues with 4 M guanidine hydrochloride. A consistent finding in organ cultures with macular corneal dystrophy was the diminished synthesis of keratan sulfate proteoglycan, and this was accompanied by the production of a glycoprotein of lower MW with oligosaccharide side chains. A comparable amount of incorporated radioactivity was extracted with 4 M guanidine hydrochloride from corneas with macular dystrophy and corneas of controls. Despite this, corneas with macular dystrophy still contained abundant intra- and extracellular material with the histochemical attributes of nonextracted pathologic corneas, and this correlated with concentrations of nonextracted isotope as shown by autoradiography. Transmission electron microscopy of the guanidine hydrochloride-extracted corneas with macular dystrophy disclosed fibrillogranular material with a similar ultrastructure to the storage substance within nonextracted corneas to be located at sites of disrupted cells. Further work is needed to establish the basic defect in macular corneal dystrophy. Although it is possible that organ cultures of corneas with macular dystrophy synthesize the storage material, which characterizes the disorder, the abnormal product of the organ cultures of the dystrophic corneas may reflect an altered metabolic state of dystrophic corneal fibroblasts, caused by the excessive intracellular accumulation of the storage product that typifies macular corneal dystrophy.