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Expert ophthalmologist Associate Professor Louis Tong explains his role as a clinician and researcher investigating eye disease in Asia, and discusses some of the issues affecting the field today epithelial cell biology, inflammation and meibomiam gland dysfunction; I am the only faculty member that runs a dedicated clinical service for dry eye and related ocular surface inflammatory disorders. What are the main areas of research conducted by SERI and what types of training and development opportunities are available at the Institute? To begin, can you provide a brief overview of your academic background and describe what initially attracted you to ophthalmology and, more specifically, corneal and external eye disease? I am a principal clinician-scientist, Head of the Ocular Surface Research Group and co-Head of the Ocular Inflammation and Immunology Research group at the Singapore Eye Research Institute (SERI). I’m also a senior consultant ophthalmologist at the Corneal and External Eye Service of the Singapore National Eye Centre, as well as being tenured track Associate Professor at the Office of Clinical, Academic and Faculty Affairs at the Duke-National University of Singapore (Duke-NUS) graduate medical school. In addition, I am a senior clinical lecturer and adjunct Associate Professor at the Department of Ophthalmology, Yong Loo Lin School of Medicine, NUS, and a clinical physician on the faculty of the Singhealth Residency Program for the Ophthalmology Academic Clinical Program. I received my PhD degree from NUS, and was trained first in Singapore as an undergraduate before further training and fellowships in the UK and Baylor College of Medicine, USA. My research interests are dry eye, corneal SERI is Singapore’s premier eye research institute, focusing on the understanding and treatment of eye diseases, with particular emphasis on those typical to Asia. Its goal is to be a global centre of excellence in eye and vision research in Asia, known internationally for translating basic science to clinical applications for the prevention and treatment of sight-threatening disorders. It aims to undertake innovative and outstanding basic science and clinical research, with an emphasis on translational research, and to work closely with stakeholders and partners both nationally and internationally. SERI covers a diverse spread of eye research, including ocular surface, cornea and refractive, glaucoma, retina, neuro-ophthalmology, paediatric ophthalmology and vision research, epidemiology and health service research. It is supported by platforms such as proteomics, ocular genetics, animal models of disease, imaging, and databases and statistics. Why has there been such an increase in demand for international ophthalmic activities in recent years? Firstly, an ageing population in many countries results in increased patient load. Ophthalmology is essentially a discipline dealing with ageing problems such as senile cataracts, glaucoma, age-related macular degeneration, etc. Secondly, surgical intervention in routine problems such as cataracts has become highly effective through recent advances such as the use of phacoemulsification; more accurate refractive correction has altered many people’s lifestyles. Thirdly, increased government investment in eye care programmes and infrastructure has had an impact. In Singapore, the establishment of the Singapore National Eye Centre and later SERI was pivotal to the success of ophthalmic programmes. Fourthly, recent years have seen increased lobbying from eye research institutes for media publicity and increased funding through endowments and special interest groups. Via networking at large international meetings and events, eyecare and research have increased in reputation and prominence. Finally, technological advances in lasers and imaging technology, and breakthroughs in basic sciences, have benefited eyecare and research. Suddenly, people are realising that problems in ophthalmology can be addressed with state-of-the-art tools from other fields such as cancer, rheumatology and radiology. ASSOCIATE PROFESSOR LOUIS TONG Roving eye How is the Ocular Surface Research Group, of which you are Head, so well placed to conduct competitive research? Do you collaborate with any other partners? Apart from its work as part of the Collaborative Research Initiative in meibomiam gland dysfunction, the Group is also collaborating with many other local and overseas institutions; for example, the Victor Chang Cardiac Research Institute in Sydney, Australia, the University of California, USA, and industry organisations such as Alcon (now a Novartis company), Allergan Inc. and Santen Pharmaceuticals. You have been awarded a career support research award from the National Medical Research Council. Could you provide an overview of what your research will entail? I have been awarded the Clinician Scientist Award in the category of senior investigator. This is funding over five years to support me and my research team, in terms of manpower, equipment and consumables, to translate diagnostic and treatment modalities in ocular surface research for dry eye and eyelid inflammation into clinical care. WWW.RESEARCHMEDIA.EU 87 ASSOCIATE PROFESSOR LOUIS TONG Clear vision A prominent research group working as part of the Singapore Eye Research Institute has been conducting promising studies into diseases of the ocular surface, and so contributing to the research of a small but world-leading organisation OF ALL THE faculties natural selection has endowed the human body, one of the most precious is sight. The development of forwardfacing eyes is a landmark in human evolution as much as the opposable thumb and the ability to walk erect, and this mode of vision is an innovation around which the human body has been shaped. To a large extent it is a feature that defines humans as a species, and it is certainly one of the most integral sensory tools people use to interact with their environment on a continual moment-by-moment basis. Blindness, in part because of these considerations, must be among the most feared medical conditions humans can be affected by, as well as being difficult to cope with on a psychological and practical level. The fourth most common form of the condition worldwide is corneal blindness: functional sight loss that occurs when the cornea, the clear membrane that covers the eye, becomes scarred or vascularised to the extent that it is no longer clear. The result is that a patient can have eyes that are otherwise perfect, but be blinded by the cornea alone. SIGHT AND SINGAPORE Cornea-related blindness accounts for 10 per cent of sight loss in Asia, and is therefore a frequent focal point for ophthalmological research. The condition develops over time through episodic inflammations caused by 88INTERNATIONAL INNOVATION conditions such as dry eye syndrome, allergic keratoconjunctivitis and autoimmune scarring, or injuries including chemical damage and microbial infection. The multilayered epithelium in the ocular surface superficially resembles the skin and the special innate immune defence – the eye associated lymphoid tissue – is located here to interact with the external environment, including microbes. A key feature that has developed with evolution is its ability to react with inflammation. This limits further damage and is fine-tuned to prevent an unwarranted destructive immune response. The recruitment of immune cells to the eye and other processes relevant to systemic health is therefore governed by sensing and regulatory systems at the ocular surface. Consequently, measures which tackle inflammation and reduce corneal damage over time could have an impact on visual loss. One team hoping to achieve just such an impact is Dr Louis Tong’s Ocular Surface Research Group at the Singapore Eye Research Institute (SERI), a young organisation that nonetheless accounts for 95 per cent of Singapore’s eye publications. Through numerous collaborations, ready access to clinical populations and their own extensive expertise, Tong and his fellow scientists tackle some of the most prevalent eye diseases in Singapore, and Asia more widely. Working with the surface of the eye is an area that has its advantages, points out Tong: “The accessibility of the structure for collection Biochemical and imaging tools can be used to select dry eye patients suitable for different treatments, and even to suggest adjunctive treatments of biological materials and for surgical intervention, and consequently the opportunity to make groundbreaking collaborations are major benefits”. COLLABORATING THROUGH CORIM Recently, some of the Singapore scientist’s most influential work has been conducted alongside the Collaborative Research Initiative in Meibomian gland dysfunction (CORIM). Previous studies have shown that lipids are important for the proper function of the tear, and that imbalances result in unstable tear dynamics and dry eye. The consortium brings together four of Singapore’s leading research institutes, including SERI, in an effort to investigate the role of complex lipids in the human tear film, and the oil-secreting meibomian gland’s role in maintaining them. INTELLIGENCE A vision of the future The Singapore Eye Research Institute (SERI) Graduate Academy offers numerous programmes and scholarship opportunities, including: • Research internships with universities and polytechnics • Medical undergraduate research attachments • PhD studentships in conjunction with various universities and the National Medical Research Council, Singapore OCULAR SURFACE RESEARCH IN SINGAPORE OBJECTIVES To conduct ocular surface clinical and translational research at an internationally competitive level that aims to understand underlying mechanisms and improve treatments of ocular surface diseases. KEY PARTNERS • Short-term overseas fellowships with the National Medical Research Council and Ministry of Health Singapore Eye Research Institute (SERI) • Singhealth fellowship awards • Singapore National Eye Centre education awards Yong Loo Lin School of Medicine; Singapore Lipidomics Incubator, National University of Singapore (NUS) • Postdoctoral training fellowships NUS • Research training programmes for ophthalmic residency Singapore National Eye Centre Duke-NUS Graduate Medical School Nanyang Technological University • Various visiting professorships Ngee Ann Polytechnic, Ministry of Education The SERI Academy has also played a pivotal role in the recent establishment of the Arthur Lim Professorship in Ophthalmology, a PhD scholarship, as well as a clinician-scientist residency research programme. Bioinformatics Institute (BII); Institute of Molecular and Cell Biology; Institute of Medical Biology; Institute of Materials Research and Engineering, Agency for Science, Technology and Research (A*STAR) SERI’s responsibility within the project has been the clinical characterisation of dry eye and the pursuit of clinical trials for potential treatments, while the other institutes have analysed lipids, thermographic images of tear evaporation and meibomian gland structures. This approach has so far proved beneficial in clinical care, producing some intriguing results. For instance, based on the study, it seems that biochemical and imaging tools can be used to select dry eye patients suitable for different treatments, and even to suggest adjunctive treatments. A UNIQUE RESOURCE SERI was established in 1997 as part of the Singapore National Eye Centre, a medical facility that sees 60 per cent of the ophthalmic patients in the country. In addition to his research position, Tong runs the Centre’s dedicated dry eye service clinic, which is a referral destination for many patients in the region and beyond with challenging dry eye conditions, and serves as a recruitment point for clinical trials and studies including those performed with CORIM. Since its establishment in 2006, the clinic has gathered a database of over 1,000 dry eye patients, complete with detailed prospective clinical assessments – the largest of its kind worldwide. It is with the help of this facility that Tong and his collaborators have been able to achieve so many notable advances in the field over the last few years, including publication of the most detailed profile of ocular surface lipids to date, and helping SERI become a world leader in published papers on pterygium, a puzzling benign growth of the conjunctiva over the cornea; popularly known as ‘surfer’s eye’. They have also seen their research rapidly translated into actual therapy on a number of occasions, with projects involving the selection of eyedrops based on acidity, autologous plasma treatment for dry eye, tea tree oil therapy for demodex mite infestation and lipiflow thermopulsation treatment, among others. TG2 Equally important has been the team’s work on transglutaminase-2 (TG2) in the corneal epithelium. Just as the surface of the eye must stay moist, the corneal stroma must always be dehydrated in order to remain transparent; when the epithelial layer that protects it is breached through disease or injury, it becomes hazy and obscures vision. Hence, epithelial migration is a crucial process to maintain this first line of defence, and TG2 has an indispensable role in this migration. Tong’s team has been responsible for investigating just how it helps cells adhere to the extracellular substrate, or move, depending on necessity. In a study completed last year, the Singapore researchers investigated the role of TG2 in a murine corneal wound-healing model, as well as examining in detail its action as a regulator of related processes such as cell adhesion and migration in a culture of human corneal epithelial cells. In both models, the investigation showed that TG2 knockdown delayed wound closure – and in the human cell culture, the scientists observed that the absence of TG2 had a knock-on effect on other molecular processes, implicating other elements that may be crucial in healing. In the future, it may be studies like this that provide the key to eradicating corneal blindness and its associated morbidity. FUNDING National Medical Research Council Biomedical Research Council of Singapore CONTACT Associate Professor Louis Tong Head, Ocular Surface Research Group Co-Head, Ocular Immunology and Inflammation Research Group Head, Research Training and Development Singapore National Eye Centre 11, Third Hospital Avenue Singapore 168751 Singapore T +65 62 277 255 E [email protected] ASSOCIATE PROFESSOR LOUIS TONG graduated in 1993 from NUS, registered as a medical practitioner in 1994 and achieved accreditation with the Singapore Medical Council as an ophthalmologist in 2004. Apart from holding a tenure track regular faculty position at Duke-NUS graduate medical school and an adjunct appointment at the Yong Loo Lin School of Medicine, NUS, he currently holds several appointments at SERI, and runs a dry eye service at the Singapore National Eye Centre, focusing on tear dysfunction and meibomian gland disease, and a general eye clinic for cataract surgery. WWW.RESEARCHMEDIA.EU 89