Glaucoma is the leading cause of irreversible blindness in the world. Glaucoma is incurable, but with treatment, many patients can maintain their vision. Unfortunately, ~20% of patients with glaucoma go blind. With rising patient numbers and associated healthcare costs, there is an urgent need to identify patients at risk of blindness and accordingly allocate healthcare resources to those at highest risk. This collaboration will tackle two approaches to answer why blindness still occurs amongst patients with glaucoma: 1) new technologies to screen undiagnosed glaucoma and monitor the disease in the community; 2) targeting age-associated metabolic insufficiency in glaucoma with nicotinamide.

Cardiovascular diseases, diabetes and vision impairment are among the top leading causes of disease burden in Singapore. As population ages, the prevalence of these medical conditions and the number of people with multiple chronic diseases are rapidly increasing. Primary prevention or efficient screening of these prevalent diseases in communities represents the most cost-effective, affordable and sustainable course of action in the long run. In this project, we aim to develop cutting-edge digital and analytic technologies that will transform the ways we screen and auto-triage these three major medical conditions, based on ocular imaging.

The overall aim of our program is to develop an innovative, combinatorial cell- and polymer-based neurotrophic factors delivery platform, for validation in non-human primate retinal disease models to address unmet needs in retinal degenerative disease. It represents an unprecedented opportunity to harness the combined promise of advanced biomaterials, cutting-edge iPSC technology and robust pre-clinical validation in NHP models. We aim to advance the field of regenerative cell therapy and help develop novel therapies for otherwise incurable and blinding retinal degenerative disease.

The OrBiTAL programme is aimed at developing a hydrogel-based biomaterials platform for ocular drug delivery for the treatment retinal vascular disease, such as neovacular choroidal vascular (CNV) disease and diabetic macular oedema (DME). Our focus is to develop biodegradable and amphiphilic polymers for (1) Intravitreal sustained drug delivery of anti-VEGF biologics, (2) topical micellar eyedrops for delivery of anti-VEGF molecules to the retina, and (3) suppression of post-operative intraocular scarring such as proliferative vitreoretinopathy (PVR).

RxCell will work with IMCB, NUS, SERI to build a joint-lab focussed on developing the next-generation of stem cell therapy therapeutic products for age-related diseases. RxCell will be contributing their proprietary technologies to generate hypo-immunogenic induced pluripotent stem cells (iPSC) to complement IMCB’s expertise in regenerative medicine for retinal diseases and humanised mouse models, NUS’s expertise in age-related cell therapy strategies and SERI’s expertise in large animal disease models. The specific aims for retinal disease (led by Asst Prof Su Xinyi) include: (1) To develop iPSC cell therapy for age-related retinal diseases, (2) To develop and assess next generation hypo-immunogenic iPSC-RPE and RPC, (3) Pre-clinical assessment of retinal cells in non-human primates (SERI), and (4) To address the capacity of genetically-modified 2nd generation hypo-immunogenic iPSC-RPE and RPC to engraft and evade immune recognition. The specific aims for age-related musculoskeletal disease such as sarcopenia (led by Prof Brian Kennedy) includes: (1) To develop hypo-immunogenic iPSC-derived mesenchymal stem cell (MSC) therapy for muscle, (2) To develop cell-based therapy using iPSC-derived MSCs genetically modified either to secrete protective factors for enhancement of endogenous muscle function or to promote direct engraftment into muscle.

Rising life expectancy and increased prevalence of neurodegenerative risk factors such as stroke, obesity, and diabetes have contributed to rapid increases in the worldwide prevalence of Neurological and Sense Disorders (NSDs) such as Dementia, Parkinson’s Disease (PD) and Age-related Macular Degeneration (AMD). Given that NSDs are characterized principally by the loss of cells in the Central Nervous System (CNS) or retina (for AMD), cell-based therapies as a neurorestorative strategy represents an intuitive therapeutic approach. This proposal aims to develop a source of iPS that is “somatically pristine” and at the same time hypo-immunogenic, so that it can serve as universal donor cells for cell therapy from human umbilical cord lining (CLiPS).

Aging, characterised by a progressive loss of structural and functional integrity of tissues and organs, is the greatest risk factor for human diseases. Age-related macular degeneration (AMD), is currently one of the leading causes of visual disabilities. The centrality of the endomembrane systems in cellular functions is critically implicated in the aging process points, but it is an important yet under-explored opportunity for aging research. Given that the endomembrane systems are active biomaterials, a fundamental question is how their biophysical properties change with age. Biophysical changes in the viscosity of the cytoplasm and nucleoplasm, will profoundly influence the transport and diffusion of biomacromolecules. This will in turn directly impact diverse cellular biochemistry such as signal transduction, gene regulation, metabolism, and proteostasis. We hypothesise that their replenishment and repair likely lie at the heart of an “anti-aging effort” of the cell. We aim to study this process in terminally differentiated, non-renewable retinal pigmented epithelial (RPE) cells, as a disease model - a key target of AMD. Our findings will serve as a foundation for new antiaging and regenerative therapies, and for understanding cellular aging in general. In this ambitious yet achievable collaborative proposal, the mechanisms of aging of RPE cells, and the cellular defects underlying AMD, will be interrogated from a unique perspective. A multi-scale and multi-modality approach will be adopted which integrates single molecule and super-resolution imaging, cryo-electron microscopy/tomography (cryoEM/ET), nanotechnology, omics technologies, and theoretical modelling. Such integrative and innovative approaches applied on a wide-open and important biomedical problem make this proposal unique, and allow an unprecedented “super-resolution” investigation of systemic changes in endomembrane systems of aging and AMD-affected RPE cells.

The project aims to address key challenges faced by community-based eye care in Singapore:

1. Accessibility of community-friendly ophthalmic diagnostic devices which can be easily adopted to provide comprehensive primary eye care and screening
2. Integration of a suite of novel devices on a common digital platform, there will be reduction in skilled manpower required for a sustainable eye screening and monitoring for chronic eye diseases
3. Determine stakeholders’ acceptability and cost-effectiveness of a new model of eye care in the community

Dr Raymond Najjar is a co-founder of the BONSAI international consortium led by Prof Dan Milea (SERI). The consortium includes investigators from over 42 centers in 23 countries. The aim of the consortium is to detect brain and optic nerves abnormalities using deep learning on standard retinal photographs and other ophthalmic imaging modalities. So far, the consortium had major breakthroughs in the field of neuro-ophthalmology and neurology with publications in prestigious journals such as The New England Journal of Medicine, Neurology and Annals of Neurology concerning the detection and severity classification of papilledema and other optic neuropathies using deep learning.

ASPIRE is a NUS-SERI joint laboratory which was recently formed with the aim to bridge existing strengths in fundamental basic sciences at NUS Medicine with expertise in translational ophthalmology at the Singapore Eye Research Institute (SERI) and the Singapore National Eye Centre (SNEC). Bridging world-class research at both institutions provides an outstanding opportunity for the translation and innovation of fundamental eye and vision research into the clinical setting.

By 2030, more than 30% of Singaporeans will be aged 65 years old and above. Age-related eye conditions such as cataract and glaucoma are expected to become major causes of visual impairment, and a scalable solution to provide easier accessibility for community ophthalmology is necessary. In this project, we will develop user-friendly devices for point-of-care cataract diagnosis and glaucoma monitoring in the community.

Presbyopia is the universal age-related loss of dynamic accommodation. Current optical solutions for presbyopia do not restore dynamic focus. In this project, we will develop and evaluate novel solutions for presbyopia treatment which could improve dynamic accommodation in patients with early presbyopia.

Gene therapy for inherited retinal diseases (IRDs) has made substantial strides in recent years and there is an unprecedented opportunity to modulate the degenerative process that leads to blindness. However, most of our understanding of the genetic spectrum of IRDs is derived from Caucasian patients. By leveraging on our multi-ethnic clinical cohort, we aim to build a Clinico-Genomic Database of IRDs in NUH to gain insight into Asian-centric variants and ultimately, provide our patients access to treatments that can change the blinding course of their disease.

As inherited retinal disease are individually rare, a major challenge for therapeutic development has been the lack of a suitable disease model. We aim to use patient-derived retinal organoids to characterise in-house developed therapeutics for demonstration of reversal of the disease phenotype.

Microvascular dysfunction due to atherosclerotic risk factors can simultaneously cause damage in the brain and heart. However, separately evaluating the extent of damage in each organ system requires a battery of investigations which culminates in a significant burden on the patient and healthcare system. Retinal microvasculature, unlike microvasculature in the brain and heart, can be acquired non-invasively via retinal photography at a fraction of the time and cost. Our goal is to evaluate if retinal images can be used as a non-invasive and inexpensive stratification tool to judiciously select patients who would benefit from further neurological or cardiac investigations.

Neovascular age-related macular degeneration (nAMD) is the leading cause of irreversible blindness in elderly persons. Given the invasive nature and cost of current treatment, the search for more efficacious and durable treatment is ongoing. Our objective is to assess the anti-angiogenic properties of a novel Lyn kinase inhibitor for treating choroidal neovascularization and to determine if it has a synergistic drug effect with anti-vascular endothelial growth factor for treatment of choroidal neovascularisation.

The incidence of retinal degeneration disease including AMD is growing with aging population. Stem cell therapeutics showed promising results but limited success in restoring patients’ vision. To warrant treatment outcome, it is critical to construct a comprehensive cell scaffold supporting cell growth, surgical delivery and in vivo cell viability. We aim to develop a biodegradable and bioactive scaffold by 3D printing with mechanical robust feature to support retinal cell transplantation and long-term function. This work will be performed in parallel with our teams’ work on developing alternative stem cell resources towards first-in-man clinical trials for AMD in Singapore.

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness, due to degradation of retinal pigment epithelium (RPE) cells. Cell therapy has offered potential but limited regeneration capability because insufficient functional recovery post transplantation. We aim to develop a bioinspired and photo-protective scaffold that structurally mimics endogenous bruch’s membrane to support retinal cell transplantation and long-term function. This biomimetic matrix will optimize cell therapies by improving functional integration with the natural tissue for patients with retinal degeneration disease.