Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-26T00:12:55.797Z Has data issue: false hasContentIssue false
  • English
  • Français

Collagen Fibrils and Proteoglycans of Macular Dystrophy Cornea: Ultrastructure and 3D Transmission Electron Tomography

Published online by Cambridge University Press:  05 May 2015

Saeed Akhtar ,
Hind M. Alkatan ,
Omar Kirat ,
Adnan A. Khan  and
Turki Almubrad
Saeed Akhtar*
Affiliation:
Cornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
Hind M. Alkatan
Affiliation:
King Khalid Eye Specialist Hospital, Riyadh, Saudi Arabia
Omar Kirat
Affiliation:
King Khalid Eye Specialist Hospital, Riyadh, Saudi Arabia
Adnan A. Khan
Affiliation:
Cornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
Turki Almubrad
Affiliation:
Cornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
*
*Corresponding author.[email protected]; [email protected]
Get access

Abstract

We report the ultrastructure and 3D transmission electron tomography of collagen fibrils (CFs), proteoglycans (PGs), and microfibrils within the CF of corneas of patients with macular corneal dystrophy (MCD). Three normal corneas and three MCD corneas from three Saudi patients (aged 25, 31, and 49 years, respectively) were used for this study. The corneas were processed for light and electron microscopy studies. 3D images were composed from a set of 120 ultrastructural images using the program “Composer” and visualized using the program “Visuliser Kai”. 3D image analysis of MCD cornea showed a clear organization of PGs around the CF at very high magnification and degeneration of the microfibrils within the CF. Within the MCD cornea, the PG area in the anterior stroma was significantly larger than in the middle and posterior stroma. The PG area in the MCD cornea was significantly larger compared with the PG area in the normal cornea. The CF diameter and inter-fibrillar spacing of the MCD cornea were significantly smaller compared with those of the normal cornea. Ultrastructural 3D imaging showed that the production of unsulfated keratin sulfate (KS) may lead to the degeneration of micro-CFs within the CFs. The effect of the unsulfated KS was higher in the anterior stroma compared with the posterior stroma.

Keywords

macular corneal dystrophy3D imagingCFsPGsstroma
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 21 , Issue 3 , June 2015 , pp. 666 - 679
Copyright
© Microscopy Society of America 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abreu, E.B, Novaes, G.A. Fernandes, B.F., Odashiro, P.R., Odashiro, A.N., Parizotto, Ide O. & Burnier, M.N. Jr. (2012). Corneal stromal dystrophies: a clinical pathologic study. Arq Bras Optalmol 75, 390–393.CrossRefGoogle ScholarPubMed
Akama, T.O., Nakayama, J., Nishida, K., Hiraoka, N., Suzuki, M., McAuliVe, J., Hindsgaul, O., Fukuda, M. & Fukuda, M.N. (2001). Human corneal GlcNac 6-O-sulfotransferase and mouse intestinal GlcNac 6-O-sulfotransferase both produce keratan sulphate. J Biol Chem 276, 16271–16278.Google Scholar
Akama, T.O., Nishida, K., Nakayama, J., Watanabe, H., Ozaki, K., Nakamura, T., Dota, A., Kawasaki, S., Inoue, Y., Maeda, N., Yamamoto, S., Fujiwara, T., Thonar, E.J., Shimomura, Y., Kinoshita, S., Tanigami, A. & Fukuda, M.N. (2000). Macular corneal dystrophy type I and type II are caused by distinct mutations in a new sulphotransferase gene. Nat Gen 26, 237–241.Google Scholar
Akhtar, S., Alkatan, H., Kirat, O. & Almubrad, T. (2014). Ultrastructural and three-dimensional study of post-LASIK ectasia cornea. Microsc Res Tech 77, 91–98.CrossRefGoogle ScholarPubMed
Akhtar, S., Bron, A.J., Hawksworth, N.R., Bonshek, R.E. & Meek, K.M. (2001). Ultrastructural morphology and expression of proteoglycans, betaig-h3, tenascin-C, fibrillin-1, and fibronectin in bullous keratopathy. Br J Ophthalmol 85, 720–731.Google Scholar
Aldave, A.J., Yellore, V.S., Thonar, E.J., Udar, N., Warren, J.F., Yoon, M.K., Cohen, E.J., Rapuano, C.J., Laibson, P.R., Margolis, T.P. & Small, K. (2004). Novel mutations in the carbohydrate sulfotransferase gene (CHST6) in American patients with macular corneal dystrophy. Am J Ophthalmol 137, 465–473.Google Scholar
Birk, D.E., Fitch, J.F., Babiarz, J.P., Doane, K.J. & Linsenmayer, T.F. (1990). Collagen fibrilogenesis in vitro: Interaction of types I and V collagen regulates fibril diameter. J Cell Sci 95, 649–657.Google Scholar
Caterson, B., Christner, J.E. & Baker, J.R. (1983). Identification of a mono-clonal antibody that specifically recognizes corneal and skeletal keratan sulfate. Monoclonal antibodies to cartilage proteoglycan. J Biol Chem 258, 8848–8854.CrossRefGoogle Scholar
Chakravarti, S., Petroll, W.M., Hassell, J.R., Jester, J.V., Lass, J.H., Paul, J. & Birk, D.E. (2000). Corneal opacity in lumican-null mice: Defects in collagen fibrils structure and packing in the posterior stroma. Invest Ophthalmol Vis Sci 41, 3365–3373.Google ScholarPubMed
Cursiefen, C., Hofmann-Rummelt, C., Schlötzer-Schrehardt, U., Fischer, D.C. & Küchle, M. (2000). Immunophenotype classification of macular corneal dystrophy: First case report of immunophenotype I A outside of Saudi Arabia. A clinical histopathological correlation with immunohistochemistry and electron microscopy. Klin Monbl Augenheilkd 217, 118–126.Google Scholar
Dang, X., Zhu, Q., Wang, L., Su, H., Lin, H., Zhou, N., Liang, T., Wang, Z., Huang, S., Ren, Q. & Qi, Y. (2009). Macular corneal dystrophy in a Chinese family related with novel mutations of CHST6. Mol Vis 15, 700–705.Google Scholar
Edward, D.P., Yue, B.Y., Sugar, J., Thonar, E.J., Sunder Raj, N., Stock, E.L. & Tso, M.O. (1988). Heterogeneity in macular corneal dystrophy. Arch Ophthalmol 106, 1579–1583.Google Scholar
El-Ashry, M.F., El-Aziz, M.M., Wilkins, S., Cheetham, M.E., Wilkie, S.E., Hardcastle, A.J., Halford, S., Bayoumi, A.Y., Ficker, L.A., Tuft, S., Bhattacharya, S.S. & Ebenezer, N.D. (2000). Identification of novel mutations in the carbohydrate sulfotransferase gene (CHST6) causing macular corneal dystrophy. Inves Ophthalmol Vis Sci 43, 377–382.Google Scholar
Faran, M.F. & Tabbara, K.F. (1991). Corneal dystrophies among patients undergoing keratoplasty in Saudi Arabia. Cornea 10, 13–16.Google Scholar
Gulias-Cañizo, R., Castañeda-Díez, R., Gómez-leal, A., Klintworth, G.K. & Rodríguez-Reyes, A.A. (2006). Corneal macular dystrophy: Clinical, histopathologic and ultrastructuralfeatures. Arch Soc Esp Oftalmol 81, 315–320.Google Scholar
Jonasson, F., Oshima, E., Thonar, E.J., Smith, C.F., Johannsson, J.H. & Klintworth, G.K. (1996). Macular corneal dystrophy in Iceland. A clinical, genealogical and immunohistochemial study of 28 patients. Ophthalmology 103, 1111–1117.CrossRefGoogle Scholar
Klintworth, G.K., Oshima, E., al-Rajhi, A., al-Salif, A., Thonar, E.J. & Karcioglu, Z.A. (1997). Macular corneal dystrophy in Saudi Arabia: A study of 56 cases and recognition of a new immunophenotype. Am J Ophthalmol 124, 9–18.Google Scholar
Klintworth, G.K. & Vogel, F.S. (1964). Macular corneal dystrophy. An inherited acid mucopolysaccharide storage disease of the corneal fibroblast. Am J Pathol 45, 565–586.Google Scholar
Küchle, M., Cursiefen, C., Fischer, D.C., Schlotzer-Schrehard, U. & Naumann, G.O.H. (1999). Recurrent macular corneal dystrophy type II 49 years after penetrating keratophathy. Arch Ophthalmol 117, 528–531.CrossRefGoogle Scholar
Lang, G.K. & Naumann, G.O. (1987). The frequency of corneal dystrophies requiring keratoplasty in Europe and the U.S.A. Cornea 6, 209–211.Google Scholar
Lewis, D., Davis, Y., Nieduszynski, I.A., Lawrence, F., Quantock, A.J., Bonshek, R. & Fullwood, N.J. (2000). Ultrastructural localization of sulphated and unsulphated keratan sulphate in normal and macular corneal dystrophy type 1. Glycobiology 10, 305–312.Google Scholar
Lewis, P.N., Pinali, C., Young, R.D., Meek, K.M., Quantock, A.J. & Knupp, C. (2010). Structural interactions between collagen and proteoglycans are elucidated by three-dimensional electron tomography of bovine cornea. Structure 18, 1–7.Google Scholar
Liu, C.Y., Birk, D.E., Hassell, J.R., Kane, B. & Kao, W.W.Y. (2003). Keratocan-deficient mice display alterations in corneal structure. J Biol Chem 278, 21672–21677.Google Scholar
Meek, K.M., Quantock, A.J., Elliott, G.F., Ridgway, A.E.A., Tullo, A.B., Bron, A.J. & Thonar, E.J. (1989). Macular corneal dystrophy: The macromolecular structure of the stroma observed using electron microscopy and synchrotron X-ray diffraction. Exp Eye Res 49, 941–958.CrossRefGoogle ScholarPubMed
Mehmet, H., Scudder, P., Tang, P.W., Hounsell, E.F., Caterson, B. & Feizi, T. (1986). The antigenic determinants recognized by three monoclonal antibodies to keratan sulphate involve sulphated hepta- or larger oligosaccharides of the poly(N-acetyllactosamine) series. Eur J Biochem 157, 385–391.CrossRefGoogle ScholarPubMed
Musselmann, K. & Hassell, J.R. (2006). Focus on molecules: CHST6 (carbohydrate sulfotransferase 6; corneal Nacetylglucosamine-6-sulfotransferase). Exp Eye Res 83, 707–708.Google Scholar
Palka, B.P., Sotozono, C., Tanioka, H., Akama, T.O., Yagi, N., Boote, C., Young, R.D., Meek, K.M., Kinoshita, S. & Quantock, A.J. (2010). Structural collagen alterations in macular corneal dystrophy occur mainly in the posterior stroma. Curr Eye Res 35, 580–586.CrossRefGoogle ScholarPubMed
Pandrowala, H., Bansal, A., Vemuganti, G.K. & Rao, G.N. (2004). Frequency, distribution, and outcome of keratoplasty for corneal dystrophies at a tertiary eye care center in South India. Cornea 23, 541–546.CrossRefGoogle Scholar
Parfitt, G.J., Pinali, C., Akama, T.O., Young, R.D., Nishida, K., Quantock, A.J. & Knupp, C. (2011). Electron tomography reveals multiple self-association of chondroitin sulphate/dermatan sulphate proteoglycans in Chst5-null mouse corneas. J Struct Biol 174, 536–541.CrossRefGoogle ScholarPubMed
Parfitt, G.J., Pinali, C., Young, R.D., Quantock, A.J. & Knupp, C. (2010). Three-dimensional reconstruction of collagen–proteoglycan interactions in the mouse corneal stroma by electron tomography. J Struct Biol 170, 392–397.CrossRefGoogle ScholarPubMed
Plessy, B. & Bettelheim, F.A. (1975). Water vapour sorption of keratan sulphate. Mol Cell Biochem 6, 85–91.CrossRefGoogle Scholar
Quantock, A.J., Fullwood, N.J., Thonar, E.J., Waltman, S.R., Capel, M.S., Ito, M., Verity, S.M. & Schanzlin, D.J. (1997). Macular corneal dystrophy type II: Multiple studies on a cornea with low levels of sulphated keratan sulphate. Eye 11, 57–67.Google Scholar
Quantock, A.J., Meek, K.M., Thonar, E.J. & Assil, K.K. (1993). Synchrotron x-ray diffraction in atypical macular dystrophy. Eye 7, 779–784.CrossRefGoogle ScholarPubMed
Rada, J., Cornuet, P.K. & Hassell, J.R. (1993). Regulation of corneal collagen fibrilogenesis in vitro by corneal proteoglycan (lumican and decorin) core proteins. Exp Eye Res 56, 635–648.CrossRefGoogle Scholar
Saika, S., Shiraishi, A., Liu, C.Y., Funderburgh, J.L., Kao, C.W., Converse, R.L. & Kao, W.W. (2000). Role of lumican in the corneal epithelium during wound healing. J Biol Chem 275, 2607–2612.CrossRefGoogle ScholarPubMed
Santo, R.M., Yamaguchi, T., Kanai, A., Okisaka, S. & Nakajima, A. (1995). Clinical and histopathologic features of corneal dystrophies in Japan. Ophthalmology 102, 557–567.Google Scholar
Scott, J.E., Orford, C.R. & Hughes, E.W. (1981). Proteoglycan-collagen arrangements in developing rat tail tendon. An electron microscopical and biochemical investigation. Biochem J 195, 573–581.Google Scholar
Tickoo, S.K., Amin, M. & Zarbo, R.J. (1998). Colloidal iron staining in renal epithelial neoplasms, including chromophobe renal cell carcinoma: Emphasis on technique and patterns of staining. Am J Surg Pathol 22, 419–424.CrossRefGoogle ScholarPubMed
Yang, C.J., SundarRaj, N., Thonar, E.J. & Klintworth, G.K. (1988). Immunohistochemical evidence of heterogeneity in macular corneal dystrophy. Am J Ophthalmol 106, 65–71.Google Scholar
Young, R.D., Akama, T.O., Liskova, P., Ebenezer, N.D., Allan, B., Kerr, B., Caterson, B., Fukuda, M.N. & Quantock, A.J. (2007). Differential immunogold localisation of sulphated and unsulphated keratan sulphate proteoglycans in normal and macular dystrophy cornea using sulphation motif-specific antibodies. Histochem Cell Biol 127, 115–120.CrossRefGoogle ScholarPubMed