Professor Keith Meek

Head of Biophysics Research Group, Emeritus Professor

: Media commentator

I joined the School in January 1999 from the Open University, where I was Senior Lecturer in Physics and Co-Director of the Oxford Research Unit. I am currently Head of the Structural Biophysics Group within the School. My research programme is aimed at investigating the ultrastructure of connective tissues and in particular, the basis of the shape and transparency of the cornea. The methods used include the complementary techniques of X-ray diffraction and electron microscopy together with a range of imaging and biochemical methods. X-ray work is mostly carried out at the Diamond synchrotron source near Oxford. Much of the recent work has been involved with exploring the fine structure of the cornea and sclera, the swelling properties of these tissues, and the basis of their optical and/or mechanical function. My research has been primarily funded by four consecutive 5-year MRC programme grants. The current grant, valued at £2.4 million, aims to understand the mechanisms behind corneal pathologies and to develop therapeutic strategies for the treatment of several connective tissue disorders. I am also involved in collaborative projects aimed to develop artificial biological corneal replacements.
X-ray diffraction provides information about the packing of collagen molecules within fibrils, and about the size and arrangement of the fibrils themselves. The information is quantitative, and pertains to tissue in its physiological state. The data have therefore allowed us to make a unique contribution to the theoretical calculations of corneal light transmission and we are currently using the techniques to explain the scattering characteristics of the cornea in pathological conditions or following various surgeries including LASIK and photorefractive keratectomy. We also have an active programme inproving methods of corneal cross-linkin and set up the UK Cross-linking Consortium in 2013.

The cornea is the transparent window at the front of the eye and is its main focussing element. To fulfil its role it has to be transparent, strong and precisely shaped. Transparency and strength are controlled by the collagen fibrils that make up the cornea, and by the small molecules between them. Shape is also controlled by the collagen arrangement, but we have now discovered a complex system of small elastic fibres that we believe helps to restore shape when the cornea is distorted, for example as blood is pumped round the body, during blinking or after eye rubbing. These properties of the cornea are controlled at different structural levels: collagen molecules form fibrils, which in turn form larger structures called lamellae, which are then stacked up to form the tissue itself. Elastic fibres that contain the protein elastin are concentrated around the edge of the cornea in the form of sheets, which we have shown are connected across the human cornea by fine filaments rich in proteins called fibrillins. The cornea is one of the most transplanted tissues worldwide, with more than 3,779 corneal grafts performed in 2015 in the UK alone, which represents a 51% increase since 2005; this annual rise in corneal transplantation is mirrored in developed countries with similar demographics. However, there is a severe shortage of good quality donor corneas worldwide, with over 90% of individuals with corneal blindness living in low to middle income countries. Whilst surgical intervention for vision loss is generally successful, it is not without risk of graft rejection, infection, post-operative scarring, regression of effect, and astigmatism following corneal transplantation. Given the significant socio-economic burden of corneal dysfunction and the efforts put into the alleviation and management of corneal problems by the NHS, it is imperative that we improve understanding of the underlying basis of image quality loss in disease and following surgery, and thus improve quality of life in the UK and for millions worldwide. This is the driver of our corneal research programme.

From previous work by us and others, we know a lot about why the cornea is transparent and are beginning to understand the arrangement of collagen lamellae and elastic fibres that gives rise to the cornea's shape and thus its focusing abilities. However, the contribution of different elements of the structure to the overall function is still not known and, until we elucidate this, it will not be possible to understand why, in numerous diseases of the cornea, or after different types of surgery on the cornea, transparency, strength and/or shape are abnormal and vision is lost or very blurred. We have pioneered the use of several sophisticated techniques to study the cornea at every structural level from the molecules upwards: x-ray scattering, serial block face scanning electron microscopy and two photon fluorescence light microscopy.

We are currently building equipment that will allow us to measure which constituents of the structure change when the cornea is distorted by known forces, either during its normal functioning or due to disease and/or surgery. We expect soon to explain how lamellae are arranged to provide form and strength, how the elastic fibres are structured in different parts of the cornea, and what role they play in health and disease. We showed that abnormalities of the elastic fibres occur in corneal diseases such as keratoconus, and we are testing our idea that they play a role in other diseases of the eye, such as glaucoma. In addition, we are investigating treatments for corneal disorders, for example by developing new chemical crosslinking methods. To address the world-wide shortage of donor corneas, biological artificial corneas are being developed. However, for corneal replacements to function normally, we must fully understand how nature utilises the constituents of a tissue to achieve its vital properties. This means elucidating the exact relationships between its various components and its function, including how cells communicate with other cells during development, wound healing and tissue regeneration. In the case of the cornea, the knowledge that we are obtaining by discovering the exact relationship between its various structural components and its function is crucial for our understanding of corneal transparency and biomechanical stability as related to corneal development, surgical manipulation and implantation, and tissue engineering. Finally, we plan to demonstrate how cornea is an excellent model system for connective tissues more generally, by collaborating with other groups around the world, using our new techniques to aid our understanding of function/dysfunction in other parts of the body.

We have a multidisciplinary team and a range of collaborators who supply clinical advice, assist with our biomechanical studies, work with us on understanding corneal wound healing and regeneration and support our development of new methods to strengthen cornea tissues.

Research team

Dr Sally Hayes
Dr Philip Lewis
Dr James Bell

External Research collaborators

Diamond Light Source, Didcot, Oxfordshire, UK

TISSUE SUPPLY AND CLINICAL ADVICE

Professor Shigeru Kinoshita: Kyoto Prefectural University of Medicine, Kyoto, Japan

Professor Andrew Copp: Human Developmental Biology Resource, University College London, London, UK

Professor Paul Rooney: NHS Blood and Transplant, Liverpool, UK

Mr Mario Saldanha FRCS: Singleton Hospital, Swansea, UK

Mr Stephen Tuft MD: Moorfields Eye Hospital, London, UK

Professor Katerina Jirsova: Charles University, Prague, Czech Republic

Professor Petra Liskova: Charles University, Prague, Czech Republic

BIOMECHANICS AND MODELLING

Professor John Marshall: University College, London, UK

Professor Jun Liu: The Ohio State University, Ohio, USA

Professor Sophie Brasselet: Aix Marseille Université, Marseille, France

Professor Ahmed Elsheikh: (Technical advisor) University of Liverpool, Liverpool, UK

Professor Peter Pinsky: Stanford University, Stanford, USA

Dr Rafael Grytz: University of Alabama, Birmingham, USA

DEVELOPMENT AND REGENERATION

Professor Aled Clayton: Cardiff University, Cardiff, UK

Professor May Griffith: University of Montreal, Montreal, Canada

CROSSLINKING

Mark P. de Souza: FIBRX Tissue Repair, Cambridge, USA

Professor David O’Brart: Guys and St. Thomas’ Hospital, London, UK

Mr Daniel Gore MD: Moorfields Eye Hospital, London, UK

OTHER CONNECTIVE TISSUES

Professor Christine Le Maitre: Sheffield Hallam University, Sheffield, UK

Dr Himadri Gupta: (Technical advisor) Queen Mary, University of London, London, UK

Professor C. Peter Winlove: University of Exeter, Exeter, UK

Dr Julie Albon: Cardiff University, Cardiff UK

Professor Lygia Pereira: University of São Paulo, São Paulo, Brasil

Dr Riaz Akhtar: University of Liverpool, Liverpool, UK

Dr Mark Thompson: University of Oxford, Oxford, UK

I am now in an Emeritus role. Formerly, I was responsible for the teaching of Geometrical Optics and contributed to the postgraduate course run by WOPEC. As with all members of the School, I also actrd as tutor or project supervisor to undergraduates. I was School Research Mentor and still advise on research grant proposals. I also still supervise research students. I am Head of the Structural Biophysics Group and run my own sub-group interested in corneal ultrastructure which consists of two professors, post-doctoral research assistants and postgraduate students. I am responsible for the electron microscope facilities within the School.

2020 – present Cardiff University, Emeritus Professor

2021-present Guest Professor, Eye Ear Nose & Throat Hosptal, Fudan University, Shanghai, China

1999 -2020 Cardiff University, Department of Optometry and Vision Sciences, Professor of Biophysics

1999 -2003 Open University, Visiting Professor of Physics

1996 -2003 University of London, Honorary Research Fellow, St Thomas’ Hospital,

1995 - 1999 Co-director, Oxford Research Unit

1994 - 1999 Open University Senior Lecturer

1989 – 2005 University of Oxford, Honorary Research Fellow, Nuffield Dept of Ophthalmology

1988 - 1993 Open University, Wellcome Lecturer

1976 - 1988 Open University, Research Fellow

PhD SUPERVISION

Dr Sean Ashjworth (2022) Dr Ben Rumney (2020) Dr Saleha Al-Atawi (2019) Dr Eleanor Feneck (2019) Dr Camilla Phillips (2019) Dr Nada Aldahawi (2018) Dr Stephanie Campbell (2018) Dr Tomas White (2017) Dr Steven Gardner (2015) Dr Sian Morgan (2014) Ms Patrycja Borkowska M Phil (2013) Dr Simon Goodson (2013) Dr Hannah Jones (2013) Dr Erin Dooley (2012) Dr Leona Ho (2011) Dr Tom Duncan (2011) Dr Tariq Alhamad (2011) Dr Barbara Palka (2010) Dr James Doutch (2009) Dr Jack Sheppard (2008) Dr Mohammad Abahussin (2008) Dr Christina Kamma-Lorger (2007) Dr Nicola Beecher (2006) Dr Melody Liles (2006) Dr Abdullah Assiri (2005) Dr Sally Hayes (2005) Dr Veronique Seigler (2003) Dr Shukria Khan (2003) Dr Moses Otunga (2002) Dr Che Connon (2000) Dr Nicola Rodda (2000) Dr Julia Hadley (1999) Dr Maxim Totrov (1999) Dr Yifei Huang (1996) Dr Daniel Leonard (1996) Dr Nageena Malik (1993) Dr Ian Rawe (1993) Dr Nigel Fullwood (1992) Dr Andrew Quantock (1991) Dr Rita Wall (1990) Dr Tracy Gyi (1988)

INVITED LECTURES

Below are a selection of the international meetings to which I have been an invited or keynote speaker:

Int. symposium of Biology of Collagen, Aarhus, Denmark 1978
4th Pfefferkorn Conference on The Science of Biological Specimen Preparation for Microscopy and Microanalysis, Grand Canyon, USA. 1985
Association for Research in Vision and Ophthalmology Meeting, Sarasota, USA. 1987
International Conference on Eye Research, San Francisco, USA. 1988
Association for Eye Research Meeting, La Grande Motte, France.1989
10th International Conference on Eye Research, Helsinki, Finland. 1990
11th International Conference on Eye Research, Stresa, Italy. 1992
12th International Conference on Eye Research, New Delhi, India 1994
13th International Conference on Eye Research, Paris. 1998
"Through the looking glass" symposium on the cornea. Schepens Eye Research Institute, Boston, USA, 1999.
ARVO minisymposium – wound healing. Florida. 2000
Heriditary Eye Diseases (celebrating the 70th birthday of Pro. G. Klintworth), Duke University, Durham N. Carolina. 2002
EVER symposium, Alicante. 2002
World Cornea Congress, Washington DC. 2005
ESCRS Meeting, Lisbon. 2005
EVER symposium, Vilamoura, Portugal. 2005
Keratoconus Meeting, Bilbao, Spain. 2006
Keynote speaker at Keratocyte Club meeting, ARVO, Ft. Lauderdale. 2006
Japan Partership Award Meeting, Kyoto, Japan. 2006
ARVO minisymposium – collagens in the eye . Ft Lauderdale. 2007
Eukeratoconus Congress, Toulouse. 2007
Key-note speaker in the course "Refractive surgery and quality of vision" part of the Joint interuniversity master on visual science" (Master interuniversitario en ciencias de la vision). Madrid 2008
19th International Conference on Eye Research, Beijing, China. 2008
American Academy for the Advancement of Science, Chicago. 2009
ESCRS Meeting, Barcelona. 2009
Prague Ophthalmology Meeting. 2009
Gordon Conference on Cornea (Ventura, Ca USA) – pulled out due to wife’s ill health. 2010
ESCRS (Paris) – pulled out due to wife’s ill health – talk given by colleague. 2010
ARVO minisymposium – Small leucine-rich proteoglycans. Ft Lauderdale, USA. 2011
Keynote Seaker Invitation, ESRF Meeting, Grenoble. 2012
Heraeus-Seminar "Physics of the Extracellular Matrix" Bad Honnef. 2012
8th International Congress of Corneal Cross-Linking, Geneva. 2012
ARVO Education Course”Predicting, measuring and treating changes in corneal biomechanics” Seattle, Washington. 2013
ARVO symposium “Architecture of the Eye: Structural Biology and Vision" Seattle, Washington. 2013
Gordon Research Conference, Cornea Biology and Pathology, Ventura, USA. 2014
ARVO Education Course”Predicting, measuring and treating changes in corneal biomechanics” Orlando, Florida. 2014
Emmetropia meeting, University of Crete, Heraklion. 2015
David Rich Lecture, University of Alabama. 2016

I have also been an invited speaker at 60 UK meetings or universities,

Honours and awards

GuestKey Career Indicators

First ever Wellcome Lecturer at the Open University (1988)
Director of Teaching (Physics) for several years at the Open University. Invited Fellow of the Institute of Physics for contribution to UK Physics teaching.
Royal Society/Wolfson Research Merit Award holder (RS Research Fellow) – first for Cardiff University, 2007
Founder and Chair of largest Biophysics Group in the UK.
Research results have appeared in many textbooks including:

The Eye: Basic Sciences in Practice [Saunders: ISBN-0702025410]

Adler’s Physiology of the Eye [Saunders: ISBN-0323057144]

Wolff’s Anatomy of the Eye and Orbit [Hodder Arnold: ISBN-0412410109]

Computational Modeling in Biomechanics [Springer: ISBN-9048135745]

200 full research papers – Hirsch Index 55; total citations for my research over 10331 (Jan 2021)
78 research grants totalling over £12 million including an NIH grant, the four largest grants ever awarded in Optometry (MRC programme grants), and a Wolfson/RS refurbishment grant (Redwood Building)
Supervisor of 36 successful PhD students
Served on several national committees (including BBSRC BioNAP and EPSRC college) the Diamond Users Committee, ALBA synchrotron committee (Barcelona) and the Fight for Sight Grant Allocation Panel.
Awarded DSc (Manchester, 2010), Fellowship of the Association for Research in Vision and Ophthalmology, the premier society for vision research (2010) - I was amongst the first group in the UK to achieve the status, and the first in Optometry. In 2013 I was awarded the Pearce medal for outstanding contribution to Ophthalmology I gave the prestigious David Rich Lecture, University of Alabama, in 2016.
2014 – founded the UK Cross-linking consortium http://sites.cardiff.ac.uk/ukcxl/ to bring together Ophthalmologists and Vision scientists with a common interest in corneal cross-linking: http://sites.cardiff.ac.uk/ukcxl/