Structural Matrix Changes are Prevalent in the Corneal Stroma of Mucopolysaccharidosis Type VII (Sly Syndrome)

Andrew J. Quantock, Petra Liskova, Barbara P. Palka, Katerina Jirsova, Michaklis Palos, Milan Elleder, Jiri Zeman, Christian Pinali, Carlo Knupp, Robert D Young

Research output: Contribution to conferenceAbstractpeer-review


Purpose: : To investigate if and how a defective enzymatic pathway involved in proteoglycan turnover affects extracellular matrix ultrastructure we performed a detailed study of a cornea obtained at keratoplasty from a 22-yr-old man with mucopolysaccharidosis type VII (MPS VII; Sly Syndrome).

Methods: : Molecular genetic analyses and assessments of enzyme activity were performed prior to surgery. After keratoplasty proteoglycan-collagen interactions throughout the stroma were studied by transmission electron microscopy and three-dimensional electron tomography. Proteoglycans were contrasted by inclusion of Cuprolinic blue in the primary fixative.

Results: : Analysis of the GUSB gene revealed compound heterozygosity for two missense mutations c.[155C>T]+[1120C>T] leading to amino acid changes p.Ser52Phe and p.Arg374Ser. Functionally, β-glucuronidase activity in isolated leucocytes was <2 % of controls. Electron microscopy revealed a morphologically normal epithelium which overlay an atypical epithelial basement membrane-Bowman’s layer. Keratocytes were packed with cytoplasmic vacuoles containing Cuprolinic blue-positive material, and three-dimensional electron tomography revealed proteoglycans in the MPS VII stroma which were much larger than in normal cornea and formed extended linkages with multiple collagen fibrils, rather than short cross-bridge connections. Collagen fibril diameter in the MPS VII stroma was less than in normal cornea and varied considerably throughout anterior (14-32nm), mid (13-42nm) and posterior (17-39nm) stroma.

Conclusions: : Cellular changes in the MPS VII cornea resemble those in other MPS, however, a diversity in collagen fibril diameter throughout the stroma and extensive interactions with supranormal-sized proteoglycan structures may be unique features of this disorder. The data suggests that an accumulation of chondroitin-, dermatan- and heparan sulphate glycosaminoglycans in the absence of ß-glucuronidase-mediated degradation can modulate collagen fibrillogenesis.
Original languageEnglish
Publication statusPublished - 2011
EventARVO 2011 Annual Meeting - Fort Lauderdale, FL, USA
Duration: 1 Jan 1824 → …


ConferenceARVO 2011 Annual Meeting
CityFort Lauderdale, FL, USA
Period1/01/24 → …


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