Large Proteoglycan Complexes and Disturbed Collagen Architecture in the Corneal Extracellular Matrix of Mucopolysaccharidosis Type VII (Sly Syndrome)

Young, Robert David ORCID: https://orcid.org/0000-0002-8300-8002, Liskova, P., Pinali, Cristian, Palka, Barbara Paulina, Palos, M., Jirsova, K., Hrdlickova, E., Tesarova, M., Elleder, M., Zeman, J., Meek, Keith Michael Andrew ORCID: https://orcid.org/0000-0002-9948-7538, Knupp, Carlo ORCID: https://orcid.org/0000-0001-9127-2252 and Quantock, Andrew James ORCID: https://orcid.org/0000-0002-2484-3120 2011. Large Proteoglycan Complexes and Disturbed Collagen Architecture in the Corneal Extracellular Matrix of Mucopolysaccharidosis Type VII (Sly Syndrome). Investigative Ophthalmology & Visual Science 52 (9) , pp. 6720-6728. 10.1167/iovs.11-7377

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Optometry and Vision Sciences
Subjects:	R Medicine > RE Ophthalmology
Additional Information:	Confirmation received by publisher on 21 February 2014 that publisher's pdf can be self-archived 6 months after publication.
Publisher:	Association for Research in Vision and Ophthalmology
ISSN:	0146-0404
Date of First Compliant Deposit:	30 March 2016
Last Modified:	27 Sep 2023 16:17
URI:	https://orca.cardiff.ac.uk/id/eprint/18885

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