Decreased GlcNAc 6-O-sulfotransferase activity in the cornea with macular corneal dystrophy

PURPOSE. Macular corneal dystrophy (MCD) is an autosomal recessive inherite d disorder that is accompanied by corneal opacity. Explants from MCD-affect ed corneas have been reported to synthesize low-sulfated KS, suggesting tha t sulfate groups attached to KS may play critical roles in maintaining corn eal transparency. To clear the biosynthetic defect in the MCD cornea, sulfo transferase activities were determined that are presumably involved in the biosynthesis of KS: galactose-6-sulfotransferase (Gal6ST) activity and N-ac etylglucosamine 6-O-sulfotransferase (GlcNAc6ST) activity. METHODS. Gal6ST and GlcNAc6ST activities, which mere contained in the corne al extracts from corneas affected by MCD and keratoconus and from normal co ntrol corneas, were determined by measuring the transfer of (SO4)-S-35 from [S-35]3'-phosphoadenoSine 5'-phosphosulfate into the Gal residue of partia lly desulfated KS and the nonreducing terminal GlcNAc residue of GlcNAc bet a1-3Gal beta1-4GlcNAc (oligo A), respectively. RESULTS. The level of Gal6ST activity in corneal extracts from eyes with MC D, which was measured by using partially desulfated KS as an acceptor, was nearly equal to that in eyes with keratoconus and normal control eyes, in c ontrast, GlcNAc6ST activity in the extracts from MCD-affected corneas, whic h was measured by using oligo A as an acceptor, was much lower than in thos e in corneas with keratoconus and in normal control corneas. CONCLUSIONS. The decrease in GlcNAc6ST activity in the cornea with MCD may result in the occurrence of low- or nonsulfated KS and thereby cause cornea l opacity.