黄斑角膜营养不良：无法合成成熟的硫酸角质素蛋白聚糖。
Macular corneal dystrophy: failure to synthesize a mature keratan sulfate proteoglycan.
作者信息
Hassell J R, Newsome D A, Krachmer J H, Rodrigues M M
出版信息
Proc Natl Acad Sci U S A. 1980 Jun;77(6):3705-9. doi: 10.1073/pnas.77.6.3705.
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.
在手术中从黄斑角膜营养不良患者获取的角膜标本，以及在尸检时从对照眼获取的角膜标本，被置于含有糖蛋白和蛋白聚糖放射性前体的培养基中进行培养。通过分子筛色谱法和特定酶对生物合成放射性标记的物质进行提取和表征。对照角膜中的细胞合成了一种硫酸软骨素蛋白聚糖和一种硫酸角质素蛋白聚糖，类似于猴和牛角膜中存在的那些。黄斑角膜中的细胞合成了正常的硫酸软骨素蛋白聚糖，但既不合成硫酸角质素也不合成成熟的硫酸角质素蛋白聚糖。相反，黄斑角膜合成了一种具有异常大寡糖侧链的糖蛋白。这种糖蛋白在正常角膜中未被检测到，且略小于正常的硫酸角质素蛋白聚糖。无法合成成熟的硫酸角质素蛋白聚糖可能会导致角膜混浊并导致失明。由于有证据表明角膜硫酸角质素蛋白聚糖通常是通过糖蛋白中间体合成的[哈特，G. W. & 伦纳兹，W.（1978年）《生物化学杂志》253 - 5795 - 5801]，黄斑角膜营养不良可能是糖蛋白加工过程中的一种缺陷。
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