Dr Rob Young
Research Fellow, School of Optometry and Vision Sciences
Mae'r cynnwys hwn ar gael yn Saesneg yn unig.
My research centres around the application of electron optical techniques, especially transmission and scanning electron microscopy, to investigate the ultrastructure of connective tissues. The overarching hypothesis for my work has been that composition and structure of tissue matrices define tissue function. In the past I have worked in the field of musculo-skeletal biology, investigating the fine structure of ligaments and cartilage, to try to understand the changes within these tissues in degradative diseases such as osteo- and rheumatoid arthritis. For the past ten years I have worked in collaboration with Professor Andrew Quantock focussing on ocular tissues, including cornea, sclera and trabecular meshwork. A range of tissues obtained from human eyes, through both local and international collaborations, have been investigated to characterise the nature of interactions between collagens and proteoglycans in health and disease.
Our studies have involved a number of cutting edge technologies for microscopy, both in relation to new preparation techniques for tissue preparation, for example using low temperature tissue preservation (high pressure freezing and freeze substitution), and novel instrumentation for image acquisition (serial block face 3View ® SEM). Throughout my career I have maintained a keen interest in new methodology for electron microscopy. I have applied specialised localisation methods employing specific antibody markers to identify minute differences in tissue components, proteoglycans, during development of the cornea in the embryo. These appear to be important for the maturation of a transparent matrix, itself essential for vision. The same tissue molecules are also involved in the pathogenesis of certain blinding conditions where enzyme deficiencies gives rise to opacities in the cornea, eventually requiring a corneal transplant for treatment.
Currently there is enormous interest in 3D imaging techniques, not only in diagnostic imaging such as with OCT, but also at the level of single cells and matrix macromolecules. These methods of electron tomography and, most recently, serial block face scanning electron microscopy are being used in our electron microscopy laboratory in the Structural Biophysics Research Group.
I currently assist with laboratory-based teaching of postgraduate research students and undergraduates carrying out final year research projects.
Young, RD, Knupp, C, Pinali, C, Png, K MY, Ralphs, J R, Bushby, AJ, Starborg, T, Kadler, KE, Quantock AJ. 2014. Three-dimensional aspects of matrix assembly by cells in the developing cornea Proceedings of the National Academy of Sciences 111 (2) 687-692
Young, RD, Liskova, P, Pinali, C, Palka, BP, Palos, M, Jirsova, K, Hrdlickova, E, Tesarova, M, Elleder, M, Zeman, J, Meek, KM, Knupp, C and Quantock, AJ. 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) 6720-6728.
Young, RD, Swamynathan, SK, Boote, C, Mann, M, Quantock, AJ, Piatigorsky, J, Funderburgh, JL, Meek, KM. 2009. Stromal Edema in Klf4 Conditional Null Mouse Cornea Is Associated with Altered Collagen Fibril Organization and Reduced Proteoglycans. Investigative Ophthalmology & Visual Science 50 (9) 4155-4161
Young, RD, Akama, TO, Liskova, P, Ebenezer, ND, Allan, B, Kerr, B, Caterson, B, Fukuda, MN, Quantock, AJ. 2007. Differential immunogold localisation of sulphated and unsulphated keratan sulphate proteoglycans in normal and macular dystrophy cornea using sulphation motif-specific antibodies. Histochemistry and Cell Biology 127 (1), 115-120
Young, RD, Quantock, AJ, Sotozono, C, Koizumi, N, Kinoshita, S. 2006. Sulphation patterns of keratan sulphate proteoglycan in sclerocornea resemble cornea rather than sclera. British Journal of Ophthalmology 90 (3), 391-393
Current Research Projects
* Structural studies of cornea after freezing with a new prototype cryoprobe.
* 3D reconstruction of keratocytes and extracellular matrix in developing avian cornea by serial block face scanning electron microscopy to investigate corneal stromal development.
* Comparative ultrastructural investigation of the trabecular meshwork in normal and glaucomatous human eyes.
* Microscopical studies of corneal endothelial cells in Fuchs corneal endothelial dystrophy.
Quantock AJ (PI), K Meek & C Tucker: £836,976. A physical characterisation of assembly mechanisms and light transmission in the cornea. EPSRC project grant. 2008 – 2011
Professor Shigeru Kinoshita, Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Professor Noriko Koizumi, Centre for Regenerative Medicine, Department of Biomedical Engineering, Doshisha University, Kyoto, Japan: A New Minimally Invasive Surgery for the Treatment of Corneal Endothelial Disease
Tissue engineering and repair expertise
- Ultrastructure of connective tissue matrices, particularly in the eye and synovial joint.
- Interaction of collagens and proteoglycans in connective tissue matrix of cornea, sclera, articular cartilage and ligament.
- Regulation of corneal transparency by tissue macromolecules.
- Development of low temperature tissue processing techniques for examination of hydrated tissue ultrastructure.
- Corneal development: establishment of corneal lamellar architecture by embryonic keratocytes.
- Development of new non-invasive surgical modalities to treat corneal endothelial disorders.
- Application of 3D scanning electron microscopy (SEM) methods (focused ion beam-and automated serial section-SEM), for large volume 3D reconstruction of ocular connective tissue matrices.
- Structural analysis of artificial matrices for corneal replacement."