Large proteoglycan complexes and disturbed collagen architecture in the corneal extracellular matrix of mucopolysaccharidosis type VII (Sly syndrome).
Large proteoglycan complexes and disturbed collagen architecture in the corneal extracellular matrix of mucopolysaccharidosis type VII (Sly syndrome).
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DOI：
10.1167/iovs.11-7377
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发表时间：
2011-08
影响因子：
4.4
通讯作者：
R. Young;P. Lišková;C. Pinali;B. Palka;M. Palos;K. Jirsova;E. Hrdličková;M. Tesařová;M. Elleder;J. Zeman;K. Meek;C. Knupp;A. Quantock
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文献类型：
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作者：
R. Young;P. Lišková;C. Pinali;B. Palka;M. Palos;K. Jirsova;E. Hrdličková;M. Tesařová;M. Elleder;J. Zeman;K. Meek;C. Knupp;A. Quantock
蛋白多糖（PG）代谢酶的缺陷是导致一些罕见的粘多糖沉积症（MPS）的基础，对其进行研究有助于了解PG在角膜基质生物学中的作用。在此，作者分析了MPS VII（Sly综合征）的新病理变化，以确定基质超微结构中PG-胶原结合的性质。方法采用透射电子显微镜和电子断层扫描技术研究了一名22岁男性MPS VII患者角膜移植术后的PG-胶原结构和相互作用，MPS VII是由GUSB基因的复合杂合突变引起的。结果透射电镜下可见MPS VII上皮基底膜和Bowman层形态不典型。角膜细胞中充满含有异常糖胺聚糖（GAG）物质的细胞质空泡，胶原纤维比正常角膜中的胶原纤维更细，并且在MPS VII基质的前部（14-32 nm）、中部（13-42 nm）和后部（17-39 nm）区域变化很大。在三维中观察的PG在外观上是惊人的，因为它们显著大于正常角膜中的PG，并与多个胶原纤维形成高度延伸的连接。结论：MPS VII角膜的细胞变化与其他MPS相似。然而，广泛的胶原纤维直径在整个基质和广泛的基质存在的超正常大小的PG结构似乎是这种疾病的独特功能。研究结果表明，在不存在β-葡萄糖醛酸酶介导的降解的情况下，基质软骨素、皮肤素和乙酰肝素硫酸糖胺聚糖的积累可以调节胶原纤维形成。
PURPOSE Deficiencies in enzymes involved in proteoglycan (PG) turnover underlie a number of rare mucopolysaccharidoses (MPS), investigations of which can considerably aid understanding of the roles of PGs in corneal matrix biology. Here, the authors analyze novel pathologic changes in MPS VII (Sly syndrome) to determine the nature of PG-collagen associations in stromal ultrastructure. METHODS Transmission electron microscopy and electron tomography were used to investigate PG-collagen architectures and interactions in a cornea obtained at keratoplasty from a 22-year-old man with MPS VII, which was caused by a compound heterozygous mutation in the GUSB gene. RESULTS Transmission electron microscopy showed atypical morphology of the epithelial basement membrane and Bowman's layer in MPS VII. Keratocytes were packed with cytoplasmic vacuoles containing abnormal glycosaminoglycan (GAG) material, and collagen fibrils were thinner than in normal cornea and varied considerably throughout anterior (14-32 nm), mid (13-42 nm), and posterior (17-39 nm) regions of the MPS VII stroma. PGs viewed in three dimensions were striking in appearance in that they were significantly larger than PGs in normal cornea and formed highly extended linkages with multiple collagen fibrils. CONCLUSIONS Cellular changes in the MPS VII cornea resemble those in other MPS. However, the wide range of collagen fibril diameters throughout the stroma and the extensive matrix presence of supranormal-sized PG structures appear to be unique features of this disorder. The findings suggest that the accumulation of stromal chondroitin-, dermatan-, and heparan-sulfate glycosaminoglycans in the absence of β-glucuronidase-mediated degradation can modulate collagen fibrillogenesis.