Klintworth G K, Smith C F
Am J Pathol. 1977 Oct;89(1):167-82.
The inherited disorder macular corneal dystrophy (MCD), a localized corneal mucopolysaccharidosis, is currently thought to result from an inability to catabolize corneal keratan sulfate (keratan sulfate 1). As studies on isolated cells have provided insight into metabolic abnormalities in other inherited disorders, we investigated cultured corneal fibroblasts from 4 patients with MCD from several standpoints. Lines of corneal fibroblasts with MCD could not be distinguished from controls with cytochemical methods known to stain the naturally occurring accumulations. In contrast to cultured fibroblasts from patients with mucopolysaccharidoses Type I-H (Hurler syndrome) and Type II (Hunter syndrome), corneal fibroblasts from patients with MCD did not accumulate abnormal quantities of (35)S-sulfate-labeled glycosaminoglycans, but like normal corneal and cutaneous fibroblasts reached a state of equilibrium within 2 days. Also, the rate at which sulfated glycosaminoglycans were removed from cultured corneal fibroblasts in MCD by secretion and degradation more closely resembled that of normal cells than those with the systemic mucopolysaccharidoses. The secretion of sulfated glycosaminoglycans into the nutrient medium by corneal fibroblasts from patients with MCD occurred at a linear rate comparable to that of other cells studied. The aforementioned data, nonetheless, remain consistent with the hypothesis that MCD is an inherited disorder of keratan sulfate I (corneal keratan sulfate) catabolism, as isolated corneal fibroblasts in contrast to corneal explants synthesize little or no keratan sulfate in culture. In view of the latter, we also compared the profile of (35)S-labeled glycosaminoglycans produced by a corneal explant from a patient with MCD with that normally synthesized by human corneal explants. The latter synthesized and secreted a population of (35)S-sulfate-labeled glycosaminoglycans with properties of keratan sulfate. Considerably less material with these attributes was identified with the same analytic techniques in the cornea with MCD or in its surrounding medium after the abnormal cornea had been incubated under identical conditions. In addition to manifesting an impaired synthesis of corneal keratan sulfate-like material, the cornea with MCD produced a greater percentage of chondroitin-6-sulfate than normal. These findings suggest that the synthesis of corneal keratan sulfate and other glycosaminoglycans may be altered in MCD.
遗传性疾病黄斑角膜营养不良（MCD）是一种局限性角膜黏多糖贮积症，目前认为是由于无法分解代谢角膜硫酸角质素（硫酸角质素1）所致。由于对分离细胞的研究为其他遗传性疾病的代谢异常提供了见解，我们从多个角度对4例MCD患者的培养角膜成纤维细胞进行了研究。用已知能对天然存在的沉积物进行染色的细胞化学方法，无法区分MCD角膜成纤维细胞系与对照细胞。与I-H型黏多糖贮积症（Hurler综合征）和II型黏多糖贮积症（Hunter综合征）患者的培养成纤维细胞不同，MCD患者的角膜成纤维细胞不会积累异常数量的（35）S-硫酸盐标记的糖胺聚糖，但与正常角膜和皮肤成纤维细胞一样，在2天内达到平衡状态。此外，与全身性黏多糖贮积症患者的细胞相比，MCD患者培养的角膜成纤维细胞通过分泌和降解去除硫酸化糖胺聚糖的速率更接近正常细胞。MCD患者的角膜成纤维细胞将硫酸化糖胺聚糖分泌到营养培养基中的速率呈线性，与其他研究的细胞相当。然而，上述数据仍与MCD是硫酸角质素I（角膜硫酸角质素）分解代谢的遗传性疾病这一假设一致，因为与角膜外植体相比，分离的角膜成纤维细胞在培养中合成很少或不合成硫酸角质素。鉴于此，我们还比较了MCD患者角膜外植体产生（35）S标记的糖胺聚糖的谱与人类角膜外植体正常合成的谱。后者合成并分泌了一群具有硫酸角质素特性的（35）S-硫酸盐标记的糖胺聚糖。在相同分析技术下，在相同条件下孵育异常角膜后，在MCD角膜或其周围培养基中鉴定出具有这些特性的物质要少得多。除了表现出角膜硫酸角质素样物质合成受损外，MCD角膜产生的硫酸软骨素-6-硫酸盐百分比高于正常角膜。这些发现表明，MCD中角膜硫酸角质素和其他糖胺聚糖可能发生了合成改变。
