Macular corneal dystrophy: failure to synthesize a mature keratan sulfate proteoglycan.
Corneal specimens obtained during surgery from patients with macular corneal dystrophy and obtained at autopsy from control eyes were incubated in a medium containing radioactive precursors of glycoproteins and proteoglycans. Biosynthetically radiolabeled material was extracted and characterized by using molecular sieve chromatography and specific enzymes. Cells in control corneas synthesized both a chondroitin sulfate proteoglycan and a keratan sulfate proteoglycan similar to those present in monkey and bovine corneas. Cells in macular corneas synthesized a normal chondroitin sulfate proteoglycan but did not synthesize either keratan sulfate or a mature keratan sulfate proteoglycan. Instead, macular corneas synthesized a glycoprotein with unusually large oligosaccharide side chains. This glycoprotein was not detected in normal corneas and is slightly smaller than normal keratan sulfate proteoglycan. The failure to synthesize a mature keratan sulfate proteoglycan may produce corneal opacity and result in blindness. Because of evidence indicating that the corneal keratan sulfate proteoglycan is normally synthesized through a glycoprotein intermediate [Hart, G. W. & Lennarz, W. (1978) J. Biol. Chem. 253-5795-5801], macular corneal dystrophy may be a defect in glycoprotein processing.
D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D002847:Chromatography, Agarose; D003315:Cornea / Q000032:analysis / Q000378:metabolism; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006025:Glycosaminoglycans / Q000172:deficiency*; D006801:Humans; D007632:Keratan Sulfate / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D000071234:Lumican; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000032:analysis; D011509:Proteoglycans / Q000172:deficiency*
D011508:Chondroitin Sulfate Proteoglycans; D006023:Glycoproteins; D006025:Glycosaminoglycans; C000604306:LUM protein, human; D000071234:Lumican; D010446:Peptide Fragments; D011509:Proteoglycans; D007632:Keratan Sulfate