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Translational Research Innovations in Ocular Surgery Programme

$25mil Translational and Clinical Research Grant over 5 years, by National Research Foundation.

 

 

Lead Principal Investigator:

Prof Tan Tiang Hwee, Donald
Tel    :   6772 5408
Email   :   ophtand@nus.edu.sg

 

Co-Lead Principal Investigator:

A/Prof Aung Tin
Tel    :   6227 7255
Email   :   tin_aung@nuhs.edu.sg

 

Principal Investigator(s):

Dr Louis Tong

Prof Roger Beuerman

Dr Tina Wong

Dr Jod Mehta

Dr Eranga

 

Contact Details: 

Ms Sharmila Kannan
Assistant Director,
Corporate Affairs & Research Administration

Tel    :    6322 4590
Fax   :    6323 1903
Email   :    sharmila.kannan@seri.com.sg

 

   Address :

   Singapore Eye Research Institute (SERI)
   c/o Singapore National Eye Centre
   11 Third Hospital Avenue
   Singapore 168751

 

   Website  :   http://www.seri.com.sg/

 

 

Translational Research Innovations in Ocular Surgery (TRIOS) Programme by Singapore Eye Research Institute (SERI)

 

Corneal disease is the second commonest cause of treatable blindness (12 million cases globally) and glaucoma is a leading cause of irreversible blindness world-wide. An estimated 70 million people are affected, of whom over 6 million suffer from bilateral blindness. In Singapore, glaucoma is the leading cause of irreversible blindness. Primary angle closure glaucoma, which is more prevalent in Asia compared to primary open angle glaucoma, accounts for most of the blindness caused by glaucoma. Corneal diseases related to eye infections, inflammation, ocular trauma and genetic disorders are the major causes of blindness requiring corneal transplantation. Despite being a successful procedure, current surgical outcomes are limited due to long-term graft failure and rejection, resulting in increased morbidity.

 


Damaged optic nerve from Glaucoma
Whilst both glaucoma and corneal disorders may be initially treated by medical therapy (e.g. eye drops), surgery is often necessary at some stage to prevent or delay disease progression and blindness. The long-term success of glaucoma filtration surgery and corneal transplantation surgery largely hinges on the post-operative wound healing response and its modulation. Asian eyes have a greater propensity to scar compared to Caucasian eyes. Hence the major emphasis of our TCR program focuses on developing a raft of innovative treatments to modulate wound healing in the form of drugs, lasers, novel surgical techniques and devices for the management of glaucoma and corneal diseases. These emerging new therapies are expected to greatly improve treatment outcomes.

 

Furthermore, the application of novel anti-fibrotic agents would also have far-reaching implications for wound healing and surgeries in many other medical and surgical disciplines beyond ophthalmology.

 

Specific objectives of TRIOS include the development of new wound healing drugs, novel anti-microbial peptides that possess low risk of drug resistance, new and more effective, sustained release drug delivery technology, innovative ultra-high resolution imaging devices for imaging ocular structures, advanced laser-assisted corneal transplantation surgery, clinical trials and genetic studies into the study of alternate therapy for treatment of primary angle closure glaucoma and identification of new genes in angle closure glaucoma.

 

 

Potential to Improve Healthcare:

 

  • Addresses 2 major causes of global blindness
  • Aims to deliver new therapies of high clinical impact in corneal diseases & glaucoma.
  • Develop fundamental therapeutic approaches to tackle wound healing

 

 

The TRIOS Programme encompasses a total of 5 discrete but interlinked major modules:

 


  1. Scarred cornea from infection
    Ocular Wound Healing - for glaucoma surgery and corneal surgery, including LASIK - 3 subprojects on a) new drug treatments (transglutaminase-related targets) to modulate and control wound healing in the eye after surgery, b) new defensin drugs to treat inflammation and infection in the eye, and c) new drug delivery systems to deliver these drugs into specific parts of the eye
  2. Development of new biological tissue glue for many forms eye surgery (as an alternative to sutures in the eye)
  3. Development of new ultra-high resolution imaging technologies for the front of the eye with the potential to image wound healing at the cellular level
  4. Development of advanced techniques in corneal transplantation surgeries using femtosecond lasers, and to develop novel stem cell corneal endothelial transplantation methods
  5. Extensive programme in clinical research strategies relating to primary angle closure glaucoma - development of imaging devices to screen for glaucoma, a clinical trial studying the prevention of optic nerve damage (neuroprotection) in acute angle closure glaucoma, and a study to identify Asian genes for glaucoma.

 


The TRIOS Roadmap 

 

Click for enlarged picture.

 

This TRIOS approach is well-represented by the above "TRIOS Roadmap" diagram, which depicts the clinical challenges that has to be solved, our sequential vertical approach involving translational and clinical projects targeted at solving these challenges, to the final clinically applicable outcomes which may be implemented in new diagnostic and therapeutic devices, and clinical trials. Horizontally, the integration of concurrent research programs which span corneal and glaucoma areas of ophthalmic research are also depicted. The graphic consists of a Venn diagram of two interlocking circles representing corneal and glaucoma research areas, with a central combined focus of universal translational programs in wound healing therapeutics, anterior segment drug delivery, biological surgical glue, and anterior segment imaging modalities to be explored. Final outcomes of new therapeutic and diagnostic approaches of TRIOS are depicted in purple on the roadmap.

 

The central core represents our translational and clinical approach to a series of 5 integrated core research modules focusing on a thematic program exploring biological processes occurring in wound healing, tissue repair and inflammation, with the primary aim to develop new diagnostic and therapeutic modalities for ocular surgery and the treatment of inflammatory ocular diseases. 

 

 

Members of Programme

 

SERI'S TEAM OF PIs

Principal Investigator

Project

Dr Louis Tong

Wound Healing Project

Prof Roger Beuerman

Defensins Project

Dr Tina Wong

Ocular Drug Delivery Project

Dr Jod Mehta

Biological Tissue Glue Project

Prof Roger Beuerman

Ocular Imaging Project

Prof Donald Tan

Femtosecond Laser Surgery Project

Dr Jod Mehta

Corneal Endothelial Cell Project

A/ Prof Aung Tin

Primary Angle Closure Glaucoma Project:

  1. Neuroprotection Study
  2. Angel Imaging Study
  3. Ocular Genetics Study

Dr Eranga

SERI'S TEAM OF LOCAL COLLABORATORS

A/Prof Michael Raghunath

Department Biochemistry, NUS

Prof Colin Sheppard

Division of Bioengineering, NUS

A/Prof Freddy Boey

Department of Materials Science and Engineering, NTU

A/Prof Subbu Venkatraman

Department of Materials Science and Engineering, NTU

Prof Paul Chew

Department of Ophthalmology, NUHS

Dr Wong Hon Tym

Department of Ophthalmology, TTSH

Dr Subhra Kumar Biswas

Singapore Immunology Network (SIgN), A*STAR

Dr Chandra Shekhar Verma

Bioinformatics Institute, A*STAR

A/Prof Mark Seielstad

Genome Institute of Singapore, A*STAR

Prof Konstantin Pervushin

School of Biological Sciences, NTU

SERI'S TEAM OF INTERNATIONAL COLLABORATORS

Prof Shigeru Kinoshita

Department of Ophthalmology, Kyoto Prefectural University of Medicine, Japan

A/Prof Noriko Koizumi

Research Center for Regenerative Medicine, Doshisha University, Japan

A/ Prof Michael Hauser

Department of Ophthalmology, Duke Univeristy Medical Center, USA

Prof Jonathan Crowston

Center for Eye Research Australia, University of Melbourne, Australia

Dr Paul Foster

Department of Epidemiology, Institute of Ophthalmology, UK

Prof Peng Khaw

Department of Epidemiology, Institute of Ophthalmology, UK

Prof Michal Schwartz

Department of Neuroimmunology, The Weizmann Institute of Science, Israel

Prof Michael Belkin

Incumbent of the Fox Chair of Ophthalmology, Tel Aviv University, Israel

Prof He Mingguang

Department of Ophthalmology, Zhongshan Ophthalmic Center, China

Prof Rand Allingham

Department of Ophthalmology, Duke Univeristy Medical Center, USA

A/Prof David Friedman

Wilmer Eye Institute, Johns Hopkins University, USA

Prof Josef Bille

Kirchoff-Institute for Physics, University of Heidelberg, Germany

 

 

 

Selected Publications


Tong L, Chew J, Yang H, Ang LP, Tan DT, Beuerman RW. Distinct gene subsets in pterygia formation and recurrence: dissecting complex biological phenomenon using genome wide expression data. BMC Med Genomics. 2009 Mar 10; 2:14.

 

Tan DT, Beuerman RW. Ocular surface research at the Singapore Eye Research Institute. Ocul Surf. 2009 Apr; 7(2):115-7.

 

Tong L, RW Beuerman, H Yang. Prediction of pterygium recurrence based on a set of predictor genes. eLetter IOVS. IOVS Online, 17 Feb 2009.

 

How A, Chua JL, Charlton A, Su R, Lim M, Kumar RS, Crowston JG, Wong TT. Combined treatment with bevacizumab and 5-fluorouracil attenuates the postoperative scarring response after experimental glaucoma filtration surgery. Invest Ophthalmol Vis Sci. 2010 Feb; 51(2):928-32.

 

Li J, Zhu HY, Beuerman RW. Stimulation of specific cytokines in human conjunctival epithelial cells by defensins HNP1, HBD2, and HBD3. Invest Ophthalmol Vis Sci. 2009 Feb; 50(2):644-53.

 

Zhou L, Beuerman RW, Ang LP, Chan CM, Li SF, Chew FT, Tan DT. Elevation of human alpha-defensins and S100 calcium-binding proteins A8 and A9 in tear fluid of patients with pterygium. Invest Ophthalmol Vis Sci. 2009 May; 50(5):2077-86.

 

Bai Y, Liu S, Jiang P, Zhou L, Li J, Tang C, Verma C, Mu Y, Beuerman RW, Pervushin K. Structure-dependent charge density as a determinant of antimicrobial activity of peptide analogues of defensin. Biochemistry. 2009 Aug 4; 48(30):7229-39.

 

Seet LF, Su R, Barathi VA, Lee WS, Poh R, Heng YM, Manser E, Vithana EN, Aung T, Weaver M, Sage EH, Wong TT. SPARC Deficiency Results in Improved Surgical Survival in a Novel Mouse Model of Glaucoma Filtration Surgery. PLoS One. 2010 Feb 25; 5(2):e9415.

 

Wong HT, Lim MC, Sakata LM, Aung HT, Amerasinghe N, Friedman DS, Aung T. High-definition optical coherence tomography imaging of the iridocorneal angle of the eye. Arch Ophthalmol. 2009 Mar; 127(3):256-60.

 

Wong HT, Chua JL, Sakata LM, Wong MH, Aung HT, Aung T. Comparison of slitlamp optical coherence tomography and scanning peripheral anterior chamber depth analyzer to evaluate angle closure in Asian eyes. Arch Ophthalmol. 2009 May; 127(5):599-603.