Macular corneal dystrophy: failure to synthesize a mature keratan sulfate proteoglycan.

Abstract

Corneal specimens obtained during surgery from patients with macular corneal dystrophy and 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 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 keratan sulfate or a mature keratan sulfate proteoglycan. The 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. Since the corneal keratan sulfate proteoglycan apparently is normally synthesized through a glycoprotein intermediate, macular corneal dystrophy may result from a defect in glycoprotein processing.