title: Large proteoglycan complexes and disturbed collagen architecture in the corneal extracellular matrix of mucopolysaccharidosis type VII (Sly syndrome).
abstract: OBJECTIVE
  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.
authors: Structural Biophysics Group, School of Optometry and Vision Sciences, Cardiff University, Cardiff, Wales, United Kingdom.
authors: Robert D
authors: RD
authors: Young
authors: Petra
authors: P
authors: Liskova
authors: Christian
authors: C
authors: Pinali
authors: Barbara P
authors: BP
authors: Palka
authors: Michalis
authors: M
authors: Palos
authors: Katerina
authors: K
authors: Jirsova
authors: Enkela
authors: E
authors: Hrdlickova
authors: Marketa
authors: M
authors: Tesarova
authors: Milan
authors: M
authors: Elleder
authors: Jiri
authors: J
authors: Zeman
authors: Keith M
authors: KM
authors: Meek
authors: Carlo
authors: C
authors: Knupp
authors: Andrew J
authors: AJ
authors: Quantock
mesh_terms: D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D003094:Collagen / Q000378:metabolism*; D003315:Cornea / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D016039:Corneal Transplantation; D055032:Electron Microscope Tomography; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D016538:Mucopolysaccharidosis VII / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D046912:Multiprotein Complexes / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D055815:Young Adult
chemical_list: D046912:Multiprotein Complexes; D011509:Proteoglycans; D003094:Collagen