Ocular Therapeutics & Drug Delivery

Overview

Scarring is a process that affects a wide range of conditions. Scarring disease, as well as scarring following a surgery, often result in poor outcomes and present a huge healthcare cost. Our research group focuses on understanding the fundamentals of wound healing as well as discovering and identifying key target molecules and pathways that can be further developed into new and better anti-inflammatory and anti-fibrotic therapies for the eye.

Our laboratory has developed a mouse model of glaucoma filtration surgery. The close similarities in the surgical response between human patients and the mouse model highlight the suitability of this model for studying the surgical response to known therapeutics. It also shows its validity as a platform for discovering and testing novel targets. Moreover, this mouse model and other established animal models have been instrumental in increasing our understanding of the cellular and molecular biology of a wound’s healing response following ocular injury.

Our other major focus is the development of sustained release systems for the delivery of ocular therapeutics, which include antibodies, small molecules, peptides, drugs and gene therapy. In collaboration with the Schools of Materials Science and Engineering and Biochemical Engineering at the Nanyang Technological University, novel delivery systems have been successfully trialed on humans. In particular, a sustained delivery system using nanoliposome carriers to replace daily eyedrops for treating glaucoma has been licensed to a start-up company, Peregrine Ophthalmic. A Phase 2a trial in the US has also already been completed. This technology was awarded the prestigious President's Technology Award in 2014. Other collaborators include Duke NUS, IMB A*STAR, and industry partners.

Other delivery systems are also currently in the pipeline, including the delivery of siRNA and steroids for scarring and inflammation respectively. The aim of this research is to develop new sustained drug release formulations for ophthalmic conditions needing long term and/or an intensive drug regime to improve patient compliance.

Projects

Developing a sustained delivery system for silencing RNAs to treat ocular fibrosis after glaucoma filtration surgery in collaboration with NTU
Development of liposomal tacrolimus deliver system for allergic eye disease with NTU
Identifying pro-inflammatory therapeutic targets contributing to fibrosis
Evaluation of liposome steroids for treatment of ocular inflammation in collaboration with Enceladus and the University of Utrecht
Evaluation of multi-photon imaging for quantification of fibrosis with HistoIndex
Evaluation of a proprietary target for the treatment of fibrosis and IOP lowering glaucoma with Duke NUS
The evaluation of IL-11 Ab for ocular fibrosis in collaboration with Duke NUS
Development and in vivo testing of sustained release drug delivery systems for dermal fibrosis in collaboration with NTU.

Publications (Selected)

Wong CW, Czarny B, Metselaar JM, Ho C, Ng SR, Barathi AV, Storm G, Wong TT Evaluation of subconjunctival liposomal steroids for the treatment of experimental uveitis. May 2018 Sci Rep
Liu YC, Ng AHC, Ng XW, Yan P, Venkatraman SS, Mehta JS, Wong TT. Evaluation of a sustained-release prednisolone acetate biodegradable subconjunctival implant in a non-human primate model. Transl Vis Sci Tech. Oct 2017
Chong RS, Chu SW, Toh LZ, Wong TT. Inhibition of monocyte chemoattractive protein-1 prevents conjunctival fibrosis in an experimental model of glaucoma filtration surgery. Invest Ophth Vis Sci. 2017 July
Layer by layer nanoparticles as an efficient siRNA delivery vehicle for SPARC silencing. Tan YF, Mundargi RC, Chen MHA, Lessig J, Neu B, Venkatraman SS, Wong TT. Small 2014 May
Wong TT, Novack GN, Natarajan JV, Ho CL, Htoon HM, Venkatraman SS. Nanomedicine for glaucoma sustained release latanoprost offers a new therapeutic option with substantial benefits over eyedrops. Drug Del and Transl Res. March 2014
Luong QM, Lei Shang, Ang M, Wong TT, Venkatraman SS. A new design and application of bioelasters for better control of intraocular pressure in a glaucoma drainage device. Adv Healthcare Materials July 2013
A Narayanaswamy, K Lee, M Zhen, J Chua, SM Chai, PY Boey, C Zheng, T Aung, S Venkatraman, TT Wong. Randomised, controlled trial of a sustained delivery formulation of 5-fluorouracil for the treatment of failing blebs. Ophthalmology, Feb 2012.
JV Natarajan, M Ang, A Darwitan, TT Wong, SS Venkratraman. Nanomedicine for glaucoma: Liposomes provide sustained release of latanoprost in the eye. Int J of Nanomed. E Pub Jan 4 2012
How A, Chua J, Charlton A, Su R, Htoon HM, Lim M, Kumar RS, Crowston JG, Wong TT Combined treatment with Bevacizumab and 5-Fluorouracil attenuates the post-operative scarring response following experimental glaucoma filtration surgery. Invest Ophthalmol Vis Sci.2010
Seet LF, Su R, Barathi VA, Lee WS, Poh R, Heng YM, Manser E, Vithana EN, Aung T, Weaver MS, Sage EH, Wong TT. SPARC deficiency results in improved surgical survival in a novel mouse model of glaucoma filtration surgery. PLoS One 2010