Publications

Modeling inherited retinal diseases using human induced pluripotent stem cell derived photoreceptor cells and retinal pigment epithelial cells

Seah I, Goh D, Banerjee A, Su X

Front Med (Lausanne). 2024 Jul 1;11:1328474. doi: 10.3389/fmed.2024.1328474. 

Inherited retinal diseases (IRDs) represent a significant group of untreatable disorders where progress is often hindered by the lack of biologically relevant human tissue models, In this comprehensive review published in Frontiers in Medicine, we provide a detailed toolkit for leveraging human induced pluripotent stem cell (iPSC) and CRISPR/Cas9 technologies to create patient-specific 2D cellular cultures and 3D retinal organoids. We explore critical considerations for establishing robust models—including somatic cell sources, isogenic control strategies, and quality control metrics—while dissecting current iPSC-based models for conditions such as Retinitis Pigmentosa and Leber congenital amaurosis. This work underscores how high-fidelity, human-centric platforms can revolutionize drug discovery and precision medicine. By aligning with the FDA Modernization Act 2.0, these advanced in vitro models offer a scalable and scientifically superior alternative to traditional animal testing, paving the way for more effective target validation and the development of transformative ocular therapies 

Multi-species single-cell transcriptomic analysis of ocular compartment regulons

Gautam P, Hamashima K, Chen Y, Zeng Y, Makovoz B, Parikh BH, Lee HY, Lau KA, Su X, Wong RCB, Chan WK, Li H, Blenkinsop TA, Loh YH.

Nature Communication. 2021 Sep 28;12(1):5675. doi: 10.1038/s41467-021-25968-8

Our research, published in Nature Communications, presents the first comprehensive multi-species single-cell transcriptomic atlas of the eye, mapping the cornea, iris, ciliary body, neural retina, RPE, and choroid. By integrating data across humans, pigs, mice, and zebrafish, we identified conserved and species-specific transcriptional regulons that govern cellular identity and function. A significant highlight of this work is the discovery of putative adult stem cell populations within the iris tissue, which exhibits high stem-cell potency and potential for regenerative applications. Furthermore, we established a high-resolution disease map and a viral-entry map—identifying receptors for pathogens like SARS-CoV-2—to provide a foundational resource for understanding ocular disorders across different compartments. This atlas offers a powerful roadmap for identifying novel therapeutic targets and understanding the molecular drivers of cell maturation, as demonstrated by our findings on the role of the transcription factor KLF7 in retinal ganglion cell development.

A bio-functional polymer that prevents retinal scarring through modulation of NRF2 signalling pathway

 Parikh BH, Liu Z, Blakeley P, Lin Q, Singh M, Ong JY, Ho KH, Lai JW, Bogireddi H, Tran KC, Lim JYC, Xue K, Al-Mubaarak A, Yang B, R S, Regha K, Wong DSL, Tan QSW, Zhang Z, Jeyasekharan AD, Barathi VA, Yu W, Cheong KH, Blenkinsop TA, Hunziker W, Lingam G, Loh XJ, Su X

Nat Commun. 2022 May 19 ; 13:30474. doi: 10.1038/s41467-022-30474-6

Our research, published in Nature Communications, introduces poly(CEP), a synthetic bio-functional polymer designed to prevent retinal scarring, or proliferative vitreoretinopathy (PVR), a primary cause of failed retinal detachment surgeries. Challenging the traditional view of polymers as inert drug carriers, poly(CEP) acts as an active therapeutic agent by shedding micelles that are internalized by retinal cells via clathrin-dependent endocytosis to activate the NRF2 signaling pathway. This molecular mechanism effectively suppresses epithelial-mesenchymal transition (EMT), hyper-proliferation, and migration—the biological drivers of fibrosis. In experimental models, poly(CEP) demonstrated superiority over standard clinical treatments, such as SF6 gas, by maintaining retinal attachment and preventing contractile membrane growth without the need for adjunct pharmacological agents. These findings highlight a transformative approach in nanomedicine, where bio-engineered materials are specifically designed to modulate intracellular signaling to treat complex wound-healing disorders and other fibrotic diseases 

Anti-Angiogenic Nanomicelles for the Topical Delivery of Aflibercept to Treat Retinal Neovascular Disease

Zhao X, Seah I, Xue K, Wong W, Tan QSW, Ma X, Lin Q, Lim JYC, Liu Z, Parikh BH, Mehta KN, Lai JW, Yang B, Tran KC, Barathi VA, Cheong KH, Hunziker W, Su X, Loh XJ

Advanced Materials. 2021 Nov 2;e2108360. doi: 10.1002/adma.202108360

Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents remains the standard of care for neovascular retinal diseases, yet the associated treatment burden and risk of sight-threatening complications underscore the need for less invasive delivery strategies. Published in Advanced Materials, this study reports the development of a polymeric nanomicelle system — composed of the triblock copolymer EPC (poly(ethylene glycol), poly(propylene glycol), and polycaprolactone) — for the topical delivery of aflibercept to the posterior segment of the eye. The nanomicelles demonstrated a 47.3% encapsulation efficiency for aflibercept, enhanced corneal penetration in ex vivo porcine models, and achieved vitreous drug concentrations above the clinically relevant IC₅₀ threshold following topical administration in murine models. In laser-induced choroidal neovascularisation models, topically applied nEPCs loaded with aflibercept produced measurable lesion regression. Notably, unloaded nEPCs also exhibited intrinsic antiangiogenic activity in vitro and ex vivo, modulating both VEGF and PDGF signalling pathways, suggesting potential synergistic effects with the encapsulated therapeutic. 

Retinal-detachment repair and vitreous-like-body reformation via a thermogelling polymer endotamponade

Liu Z, Liow SS, Lai SL, Alli-Shaik A, Holder GE, Parikh BH, Krishnakumar S, Li Z, Tan MJ, Gunaratne J, Barathi VA, Hunziker W, Lakshminarayanan R, Tan CWT, Chee CK, Zhao P, Lingam G, Loh XJ, Su X

Nat Biomed Eng. 2019 Aug;3(8):598-610. doi: 10.1038/s41551-019-0382-7.

Current internal tamponade agents used in vitreoretinal surgery function through buoyancy forces and are associated with complications including post-operative positional requirements, elevated intraocular pressure, cataract formation, and the need for surgical removal. Published in Nature Biomedical Engineering, this study describes a thermogelling polymer endotamponade that operates instead through surface tension and swelling counter-forces, offering a mechanistically distinct approach to retinal tamponade. Biocompatibility was assessed in rabbit vitrectomy models, with surgical efficacy further evaluated in a non-human primate model of retinal detachment. Notably, as the thermogel biodegrades over approximately three months post-surgery, it promotes the reformation of a vitreous-like body that recapitulates the biophysical properties of the native vitreous humour, suggesting utility not only as a surgical adjunct but as a candidate long-term vitreous substitute.