Journal ArticleDOI
Macular corneal dystrophy. Lack of keratan sulfate in serum and cornea.
Gordon K. Klintworth,R. Meyer,R. Dennis,A. T. Hewitt,E. L. Stock,Mary Ellen Lenz,John R. Hassell,Walter J. Stark,Klaus E. Kuettner,E J Thonar +9 more
- Vol. 7, Iss: 3, pp 139-143
TLDR
Keratan sulfate in the serum appears to be derived predominantly from the normal turnover of cartilage, and these studies strongly suggest that the defect in keratan sulfates synthesis in MCD is not restricted to corneal cells and that M CD is one manifestation of a systemic disorder of keratan sulfur.Abstract:
An ELISA assay using a monoclonal antibody (ET-4-A-4) that recognizes a sulfated carbohydrate epitope in both keratan sulfate type I (corneal) and type II (skeletal) was employed to quantify keratan sulfate in serum and corneal tissue from patients with macular corneal dystrophy (MCD). This assay disclosed significant quantities of keratan sulfate in the serum in 45 healthy individuals (251 +/- 78 ng/ml), and in 66 patients with various corneal diseases (273 +/- 101 ng/ml). In contrast keratan sulfate was not detected (less than 2 ng/ml) in the serum of 16 patients with histopathologically confirmed MCD. Keratan sulfate was also detected in extracts of normal corneas and corneal tissue with a variety of pathologic conditions, but was virtually absent in corneal tissue from five patients with MCD. In corneas with MCD the chondroitin sulfate/keratan sulfate ratio was considerably higher than that of all normal and pathologic corneas studied. Since keratan sulfate in the serum appears to be derived predominantly from the normal turnover of cartilage these studies strongly suggest that the defect in keratan sulfate synthesis in MCD is not restricted to corneal cells and that MCD is one manifestation of a systemic disorder of keratan sulfate. The cartilage changes, however, do not have clinical significance. Moreover, since keratan sulfate can be detected in the blood of newborns it should be possible to diagnose MCD prior to corneal opacification.read more
Citations
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Journal ArticleDOI
Lumican Regulates Collagen Fibril Assembly: Skin Fragility and Corneal Opacity in the Absence of Lumican
Shukti Chakravarti,Terry Magnuson,Jonathan H. Lass,Karl J. Jepsen,Christian LaMantia,Heidi Carroll +5 more
TL;DR: A crucial role is established for lumican in the regulation of collagen assembly into fibrils in various connective tissues and the development of a highly organized collagenous matrix and corneal transparency.
Journal Article
Corneal Opacity in Lumican-Null Mice: Defects in Collagen Fibril Structure and Packing in the Posterior Stroma
Shukti Chakravarti,Walter M Petroll,John R. Hassell,James V. Jester,Jonathan H. Lass,Jennifer Paul,David E. Birk +6 more
TL;DR: Observations indicate a key role for lumican in the posterior stroma in maintaining normal fibril architecture, most likely by regulatingfibril assembly and maintaining optimal KS content required for transparency.
Journal ArticleDOI
Macular corneal dystrophy type I and type II are caused by distinct mutations in a new sulphotransferase gene.
Tomoya O. Akama,Kohji Nishida,Kohji Nishida,Jun Nakayama,Jun Nakayama,Hitoshi Watanabe,Kouichi Ozaki,Takahiro Nakamura,Atsuyoshi Dota,Satoshi Kawasaki,Yoshitsugu Inoue,Naoyuki Maeda,Shuji Yamamoto,Tsutomu Fujiwara,Eugene J.-M.A. Thonar,Yoshikazu Shimomura,Shigeru Kinoshita,Akira Tanigami,Michiko N. Fukuda +18 more
TL;DR: A new carbohydrate sulphotransferase gene (CHST6), encoding an enzyme designated corneal N-acetylglucosamine-6-sulphotranferase (C-GlcNAc6ST), is identified within the critical region of MCD type I, suggesting that mutations found in type II lead to loss of cornea-specific expression of CHST6.
Journal ArticleDOI
Functions of lumican and fibromodulin: Lessons from knockout mice
TL;DR: In tissues like the tendon, where both proteoglycans are present, fibromodulin may be required early in collagen fibrillogenesis to stabilize small-diameter fibril-intermediates and lumican may be needed at a later stage, primarily to limit lateral growth of fibrils.
Journal ArticleDOI
Immunofluorescence study of corneal wound healing after excimer laser anterior keratectomy in the monkey eye.
TL;DR: The distribution of fibrinogen, fibronectin, laminin, collagen types III, IV, and VI, and keratan sulfate was determined at postoperative intervals of 24 hours, 6 days, and 1 month.
References
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Journal ArticleDOI
Quantification of keratan sulfate in blood as a marker of cartilage catabolism.
Eugene J.-M.A. Thonar,Mary Ellen Lenz,Gordon K. Klintworth,Bruce Caterson,Lauren M. Pachman,Paul B. Glickman,Robert S. Katz,John P. Huff,Klaus E. Kuettner +8 more
TL;DR: If the appearance of elevated levels of serumKS do indeed correlate with the extent of cartilage erosion or destruction in individuals with OA, measurements of serum KS levels will prove extremely useful in the assessment and diagnosis of this joint disease.
Journal ArticleDOI
Macular corneal dystrophy: failure to synthesize a mature keratan sulfate proteoglycan
TL;DR: Corneal specimens obtained during surgery from patients with macular corneal dystrophy and obtained at autopsy from control eyes were incubated in a medium containing radioactive precursors of glycoproteins and proteoglycans and characterized by using molecular sieve chromatography and specific enzymes.
Journal ArticleDOI
Biochemical changes in progressive osteoarthrosis.
TL;DR: It is postulated that the changes described are compatible with collagen and matrix disruption due to focal overloading and the general attempt at repair.
Journal ArticleDOI
Absence of normal keratan sulfate in the blood of patients with macular corneal dystrophy.
Eugene J.-M.A. Thonar,Roger F. Meyer,Richard F. Dennis,Mary Ellen Lenz,Brian A. Maldonado,John R. Hassell,A. Tyl Hewitt,Walter J. Stark,E. Lee Stock,Klaus E. Kuettner,Gordon K. Klintworth +10 more
TL;DR: Sulfated keratan sulfate was not detected in the serum of 16 patients with macular corneal dystrophy, but was present at normal levels in 66 patients with other cornea diseases, and this assay should prove useful in the diagnosis of macular Corneal Dystrophy.
Journal Article
Abnormalities of proteoglycans and glycoproteins synthesized by corneal organ cultures derived from patients with macular corneal dystrophy.
Klintworth Gk,Smith Cf +1 more
TL;DR: Corneas with macular dystrophy still contained abundant intra- and extracellular material with the histochemical attributes of nonextracted pathologic corneas, and this correlated with concentrations ofNonextracted isotope as shown by autoradiography.