Ocular Therapeutics & Drug Delivery

Overview

Scarring is a natural biological process that can lead to a wide range of diseases and loss of bodily functions, if gone unchecked. Scarring disease, as well as scarring following surgery, often result in poor clinical outcomes and present a huge healthcare cost and socio-economic burden. Our research focuses on understanding the fundamentals of wound healing as well as uncovering 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 suite of animal models of ocular scarring - ranging from small to large animals that can be used to comprehensively interrogate the wound healing responses to a very similar level to what is seen in the human disease of interest. State-of-the-art live imaging and the latest molecular tools that include bioinformatics support the all-important analyses.

The other major focus of the team is the development of sustained release systems for the delivery of ocular therapeutics, which include antibodies, small molecules, peptides, drugs and gene therapy. A sustained delivery system using nanoliposome carriers to replace daily eye drops for treating glaucoma that had been licensed to a start-up company has successfully completed a Phase 2a trials in the US. This technology was awarded the prestigious President's Technology Award in 2014. Collaborators include the National University of Singapore (NUS), Duke-NUS Medical School, Institute of Medical Biology (IMB) - A*STAR, and industry partners.

Other delivery systems that are also currently in development include the delivery of siRNA, drug repurposing for treating fibrosis and steroids for scarring and inflammation respectively. The aim of our research is to develop sustained drug release formulations that will improve the efficiency of treatments for ophthalmic conditions needing long term and/or an intensive drug regime.

Projects

Developing repurposed drugs and sustained delivery systems to treat ocular fibrosis after glaucoma filtration surgery
Development of delivery system for treatment of allergic eye disease
Role of macrophages in inflammation and fibrosis in collaboration with Singapore Immunology Network (SiGN) - A*STAR and Duke-NUS Medical School
Development of a drug delivery nanomedicine of steroids for treatment of ocular inflammation in collaboration with NUS
Modulating fibrosis in proliferative vitreoretinopathy in collaboration with Duke-NUS Medical School
Investigate novel cell delivery for lymphangionesis and glaucoma surgery in collaboration with NUS and Duke-NUS Medical School

Publications (Selected)

Chaw SY, Novera W, Chacko AM, Wong TTL, Venkatraman S. In vivo fate of liposomes after subconjunctival ocular delivery. J Control Release. 2020 Dec 1;329:162-174. doi: 10.1016/j.jconrel.2020.11.053. Online ahead of print.
Li-Fong Seet, Stephanie W. L. Chu, Xiao Teng, Li Zhen Toh, and Tina T. Wong. Assessment of progressive alterations in collagen organization in the postoperative conjunctiva by multiphoton microscopy. Biomed. Opt. Express 11(11), 6495-6515 (2020).
Wong CW, Cheung N, Ho C, Barathi V, Storm G, Wong TT. Characterisation of the inflammatory cytokine and growth factor profile in a rabbit model of proliferative vitreoretinopathy. Sci Rep. 2019 Oct 28;9(1):15419. doi: 10.1038/s41598-019-51633-8.
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. Sci Rep. May 2018.
Seet LF, Toh LZ, Finger SN, Chu SWL, Wong TT. Valproic acid exerts specific cellular and molecular anti-inflammatory effects in post-operative conjunctiva. J Mol Med. Nov 2018.
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.
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.