Ocular Therapeutics & Drug Delivery | Singapore National Eye Centre

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 results in poor clinical outcomes and presents a huge healthcare cost and socio-economic burden. Our research focuses on understanding the fundamentals of fibrotic remodelling as well as the associated vascular and immune cell dysfunction with the ultimate aim to uncover and identify key molecular targets and pathways that can be further developed into new and better 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 fibrovascular 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 minimally invasive, sustained drug-release systems for delivering ocular therapeutics, including antibodies, small molecules, peptides, nucleic acids, gene editing tools, 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, NTU, A*STAR, City University of Hong Kong, University of Milan, Utrecht University, 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
Modulating fibrosis in proliferative vitreoretinopathy and nAMD in collaboration with Duke-NUS Medical School
Novel therapeutic targets against fibrosis and angiogenesis
Advanced nanocarrier systems and non-viral delivery platforms in collaboration with NUS and NTU
Biomarkers for nAMD
Precision Medicine in Glaucoma Surgery – a multi modal and omics approach to achieving durable surgical success

Publications (Selected)

Chen CJ, Zhou L, Gunaratne J, Chen HT, Barathi VA, Qiu B, Alli-Shaik A, Chia RN, Lim ST, Joo C, Cheung N, Chan CM, Koh SK, Tan A, Verma RK, Fan H, Song W, Virshup D, Wong TY, Cheung GCM, Hong W, Wang X. FRZB-induced Anti-angiogenic Effect via Caveolin-1-mediated TGFβ Signalling. Nat Commun. 2026 Apr 7. Accepted.
Ang KH, Thura M, Gupta A, Tan QSW, Kuan KY, Li J, Chia PL, Qiu B, Hong JM, Guo K, Wang X, Su X, Zeng Q. Antibody Therapy against PRL3 as a Treatment for Angiogenic Eye Diseases. Nat Commun. 2025 May 23;16(1):4791.
Lim ST, Zhao X, Liu S, Zhang W, Tan Y, Mullappilly N, Swain SM, Leong ML, Rajarethinam R, Wan KF, Ruedl C, Liddle RA, Li L, Wang X. LRG1 Inhibition Promotes Acute Pancreatitis Recovery by Inducing Cholecystokinin Type 1 Receptor Expression via Akt. Theranostics. 2025 Mar 18;15(10):4247–4269. doi: 10.7150/thno.110116.
Fan Q#, Li H#, Wang X#, Tham YC, Teo KYC, Yasuda M, Lim WK, Kwan YP, Teo JX, Chen CJ, Chen LJ, Ahn J, Davila S, Miyake M, Tan P, Park KH, Pang CP, Khor CC, Wong TY, Yanagi Y, Cheung GCM, Cheng C. Contribution of Common and Rare Variants to Asian Neovascular Age-related Macular Degeneration Subtypes. Nat Commun. 2023 Sep 11;14(1):5574. doi: 10.1038/s41467-023-41256-z.
Do TC†, Lau JW†, Sun C†, Liu S†, Kha KT, Lim ST, Oon Y, Kwan YP, Ma JJ, Mu Y, Liu X, Carney TJ, Wang X* & Xing B*. Hypoxia Deactivates Epigenetic Feedbacks via Enzyme-derived Clicking Proteolysis Targeting Chimeras. Sci Adv. 2022 Dec 14. Vol 8, Issue 50. DOI: 10.1126/sciadv.abq2216.
Alli-Shaik1†, B Qiu†, SLi Lai, N Cheung, G Tan, SP Neo, A Tan, CMG Cheung, W Hong, TY Wong, X Wang*, J Gunaratne*. System-wide Vitreous Proteome Dissection Reveals Impaired Sheddase Activity in Diabetic Retinopathy. Theranostics. 2022 Sep 11;12(15):6682-6704. doi: 10.7150/thno.72947.
Murray H, Qiu B, Ho SY, Wang X. Complement Factor B Mediates Ocular Angiogenesis through Regulating the VEGF Signaling Pathway. Int J Mol Sci. 2021 Sep 3;22(17):9580. doi: 10.3390/ijms22179580.
Qiu B, Tan A, Tan YZ, Chen QY, Luesch H, Wang X. Largazole Inhibits Ocular Angiogenesis by Modulating the Expression of VEGFR2 and p21. Mar Drugs. 2021 Aug 22;19(8):471. doi: 10.3390/md19080471.
KT Pang, M Ghim, C Liu, HM Tay, CW Fhu, RN Chia, B Qiu, P Sarathchandra, A Chester, M Yacoub, F Wilkinson, R Weston, C Warboys, HH Hou, P Weinberg, X Wang. Leucine-rich α-2-glycoprotein 1 Suppresses Endothelial Cell Activation through ADAM10-mediated Shedding of TNF-α Receptor. Front Cell Dev Biol. 05 July 2021. doi.org/10.3389/fcell.2021.706143.
Kwan YP, Teo MHY, Lim JCW, Tan MS, Rosellinny G, Wahli W, Wang X. LRG1 Promotes Metastatic Dissemination of Melanoma through Regulating EGFR/STAT3 Signalling. Cancers. 2021 Jun 30;13(13):3279.
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.
Liu C, Teo M, Pek SLT, Wu X, Leong ML, Tay HM, Hou HW, Ruedl C, Moss SE, Greenwood J, Tavintharan S, Hong W and Wang X. A Multifunctional Role of Leucine-Rich α2- Glycoprotein 1 in Cutaneous Wound Healing Under Normal and Diabetic Conditions. Diabetes. 2020 Nov; 69(11): 2467-2480.
Pang KT, Ghim M, Arshad M, Wang X, Weinberg PD. Segmenting Growth of Endothelial Cells in an Orbiting 6well Plate for Mechanobiology Study. JOVE. doi: 10.3791/61817.
Seet LF, Chu SW, Teng X, Toh LZ, Wong TT. Assessment of Progressive Alterations in Collagen Organization in the Postoperative Conjunctiva by Multiphoton Microscopy. Biomed Opt Express. 2020 Oct 19;11(11), 6495-6515.
Ho SY, Kwan YP, Qiu B, Tan A, Murray HL, Barathi VA, Tan NS, Cheung CMG, Wong TY, Wahli W, Wang X. Investigating the Role of PPARβ/δ in Retinal Vascular Remodeling Using Pparβ/δ-Deficient Mice. Int J Mol Sci. 2020 Jun 20;21(12):4403.
Lio D, Chia R, Kwek M, Wiraja C, Chang H, Khadir SMA, Wang X*, Becker DL*, Xu C*. Temporal Pressure Enhanced Topical Drug Delivery through Micropore Formation. Sci Adv. 29 May 2020; Vol. 6, no. 22, DOI: 10.1126/sciadv. aaz6919.
Liu C, Lim ST, Teo M, Tan M, Kulkarni MD, Qiu B, Li A, Lal S, dos Remedios CG, Tan NS, Wahli W, Ferenczi MA, Song W, Hong W, Wang X. Collaborative Regulation of LRG1 by TGFβ1 and PPARβ/δ Modulates Chronic Pressure-overload-induced Cardiac Fibrosis. Circ Heart Fail. 2019 Dec;12(12): e005962. doi: 10.1161/CIRCHEARTFAILURE.119.005962. Epub 2019 Dec 13.
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.
Njah K, Chakraborty S, Qiu B, Arumugam S, Raju A, Pobatti A, Lakshmanan M, Tergaonkar V, Thibault G, Wang X*, and Hong W*. A Role of Agrin in the Stability of Vascular Endothelial Growth Factor Receptor-2 During Tumor Angiogenesis. Cell Rep. 2019 July 23; 28 (4): 949-965.
Qiu B, Tan A, Barathi AV, Li Y, Liu C, Murray H, Cheng W, Busoy JM, Chen QY, Sistla S, Hunziker W, Cheung CMG, Wong TY, Hong W, Luesch H, and Wang X. Apratoxin S4 Inspired by a Marine Natural Product, a New Treatment Option for Ocular Angiogenic Diseases. IOVS. 2019;60:3254–3263.
Lio DCS, Liu C, Oo MMS, Wiraja C. Teo MHY, Zheng M, Chew SWT, Wang X, Xu C. Transdermal Delivery of Small Interfering RNA with Topically Applied Mesoporous Silica Nanoparticles for Facile Skin Cancer Treatment. Nanoscale. 2019; 11 (36) 17041-17051.
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.
Than A, Liu C, Cheng H, Duong PK, Xu C, Wang X*, Chen P*. Self-implantable Double-layered Micro-drug-reservoirs for Efficient and Controlled Ocular Drug Delivery. Nat Commun. 2018 Nov 6;9(1):4433.
Lim JCW, Kwan JYL, Tan MS, Tan M, Wahli W, Wang X. PPARβ/δ-deficiency Leads to Increased Melanoma Metastasis. Int J Mol Sci. 2018 Oct;19(10):2860.
Lio D, Liu C, Wiraja C, Qiu B, Fhu CW, WangX*, Xu C* Molecular Beacon-gold Nanosensors for Leucine-rich Alpha-2-glycoprotein-1 (Lrg1) Detection in Pathological Angiogenesis. ACS Sensor. 2018 Aug 10.
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.
Boopathy GTK, Kulkarni M, Ho SZ, Boey A, Chua EWM, Barathi VA, Carney TJ, Wang X and Hong W. Cavin-2 Regulates the Activity and Stability of Endothelial Nitric Oxide Synthase (eNOS) in Angiogenesis. JBC. 2017 Sep 14. doi: 10.1074/jbc.M117.794743.
Song WH, Wang X. The Role of TGFβ1 and LRG1 in Cardiac Remodelling and Heart Failure. Biophys Rev. Mar 2015, Volume 7, Issue 1, pp 91–104.
Song WH, Fhu CW, Ang KW, Liu CH, Nurul ABJ, Lio CS, Abraham S, Moss SE, Greenwood J, Hong WJ, Wang X. The Foetal Mouse Metatarsal Bone Explant as a Model of Angiogenesis. Nat Protoc. 2015 10,1459–1473.
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. Mar 2014.
Wang X, Abraham S, McKenzie JAG, Jeffs N, Swire M, Lange CAK, Luhmann U, Bainbridge J, Zhai Z, Arthur H, Moss SE, Greenwood J. Lrg1 Promotes Angiogenesis by Modulating Endothelial TGFβ Signaling. Nature. 2013 Jul 18; 499 (7458):306-311.
Narayanaswamy A, Lee K, Zhen M, Chua J, Chai SM, Boey PY, Zheng C, Aung T, Venkatraman S, Wong TT. Randomised, Controlled Trial of a Sustained Delivery Formulation of 5-fluorouracil for the Treatment of Failing Blebs. Ophthalmology. Feb 2012.
Natarajan JV, Ang M, Darwitan A, Wong TT, Venkratraman SS. Nanomedicine for Glaucoma: Liposomes Provide Sustained Release of Latanoprost in the Eye. Int J of Nanomed. 2012 Jan 4. E Pub.
Wang X, Harris RE, Bayston LJ, Ashe HL. Type IV Collagens Regulate BMP Signalling in Drosophila. Nature. 2008;455: 72-77.