Skip to main content Accessibility help
×
Home

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

  • Saeed Akhtar (a1), Hind M. Alkatan (a2), Omar Kirat (a2), Adnan A. Khan (a1) and Turki Almubrad (a1)...

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.

Copyright

Corresponding author

* Corresponding author. akhtars@ksu.edu.sa; saeed48@hotmail.co.uk

References

Hide All
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, 390393.
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, 1627116278.
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, 237241.
Akhtar, S., Alkatan, H., Kirat, O. & Almubrad, T. (2014). Ultrastructural and three-dimensional study of post-LASIK ectasia cornea. Microsc Res Tech 77, 9198.
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, 720731.
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, 465473.
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, 649657.
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, 88488854.
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, 33653373.
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, 118126.
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, 700705.
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, 15791583.
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, 377382.
Faran, M.F. & Tabbara, K.F. (1991). Corneal dystrophies among patients undergoing keratoplasty in Saudi Arabia. Cornea 10, 1316.
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, 315320.
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, 11111117.
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, 918.
Klintworth, G.K. & Vogel, F.S. (1964). Macular corneal dystrophy. An inherited acid mucopolysaccharide storage disease of the corneal fibroblast. Am J Pathol 45, 565586.
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, 528531.
Lang, G.K. & Naumann, G.O. (1987). The frequency of corneal dystrophies requiring keratoplasty in Europe and the U.S.A. Cornea 6, 209211.
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, 305312.
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, 17.
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, 2167221677.
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, 941958.
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, 385391.
Musselmann, K. & Hassell, J.R. (2006). Focus on molecules: CHST6 (carbohydrate sulfotransferase 6; corneal Nacetylglucosamine-6-sulfotransferase). Exp Eye Res 83, 707708.
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, 580586.
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, 541546.
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, 536541.
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, 392397.
Plessy, B. & Bettelheim, F.A. (1975). Water vapour sorption of keratan sulphate. Mol Cell Biochem 6, 8591.
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, 5767.
Quantock, A.J., Meek, K.M., Thonar, E.J. & Assil, K.K. (1993). Synchrotron x-ray diffraction in atypical macular dystrophy. Eye 7, 779784.
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, 635648.
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, 26072612.
Santo, R.M., Yamaguchi, T., Kanai, A., Okisaka, S. & Nakajima, A. (1995). Clinical and histopathologic features of corneal dystrophies in Japan. Ophthalmology 102, 557567.
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, 573581.
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, 419424.
Yang, C.J., SundarRaj, N., Thonar, E.J. & Klintworth, G.K. (1988). Immunohistochemical evidence of heterogeneity in macular corneal dystrophy. Am J Ophthalmol 106, 6571.
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, 115120.

Keywords

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

  • Saeed Akhtar (a1), Hind M. Alkatan (a2), Omar Kirat (a2), Adnan A. Khan (a1) and Turki Almubrad (a1)...

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed