The Rising Challenge of Neovascular Eye Diseases in Singapore

Singapore faces a growing public health concern with vision-threatening conditions like wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME), which are leading causes of irreversible blindness, particularly among older adults and those with diabetes. Wet AMD occurs when abnormal blood vessels grow beneath the retina, leaking fluid and causing central vision loss. Diabetic macular edema, a complication of diabetic retinopathy, involves similar vascular leakage in the macula, the eye's central vision area. In Singapore, projections indicate a 42 percent increase in wet AMD prevalence by 2030, potentially straining healthcare resources with economic burdens estimated between SGD 162.9 million and SGD 20.31 billion annually. Diabetic retinopathy prevalence is notably higher among Indian and Malay populations, affecting one in 10 adults with diabetes in certain ethnic groups.

These conditions share a pathological hallmark: pathological angiogenesis, where leaky blood vessels damage retinal tissue. Current treatments rely on frequent intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs like ranibizumab or aflibercept, administered monthly into the eye. However, up to 45 percent of patients show inadequate responses, and the procedure carries risks of infection, retinal detachment, and patient discomfort.

Singapore's proactive healthcare system, bolstered by robust higher education research institutions, is addressing these challenges through innovative repurposing of existing therapies. This positions the nation as a hub for translational medicine, where academic discoveries rapidly advance to clinical applications.

From Cancer Therapy to Vision Savior: The Story of PRL3-Zumab

PRL3-zumab, a first-in-class humanized monoclonal antibody, was originally developed to target the PRL3 protein, a metastasis driver identified in 1998 by Professor Qi Zeng at A*STAR's Institute of Molecular and Cell Biology (IMCB). PRL3 overexpression promotes cancer cell migration and vascular abnormalities. Remarkably, preclinical research revealed PRL3's upregulation in diseased ocular tissues, mirroring its role in tumors.

The drug selectively binds PRL3 on diseased endothelial cells, stabilizing vessels and halting leakage without affecting healthy tissues. This tissue-specific action enhances safety, as demonstrated in Phase II cancer trials involving over 210 patients across Singapore, the US, China, and Malaysia, showing a favorable profile.

In Singapore's biotech landscape, PRL3-zumab exemplifies successful academia-industry synergy, with Intra-ImmuSG Pte Ltd, an IMCB spin-off founded by Prof. Zeng, driving commercialization. This model inspires aspiring researchers eyeing careers in drug development through platforms like higher-ed-jobs in biomedical sciences.

Breakthrough Preclinical Evidence in Nature Communications

The pivotal study, published May 23, 2025, in Nature Communications, detailed PRL3-zumab's efficacy in mouse models of choroidal neovascularization (CNV) for wet AMD and oxygen-induced retinopathy (OIR) for diabetic retinopathy. Researchers observed PRL3 upregulation in diseased choroid-retinal pigment epithelium (RPE) and retina.

In CNV models, intravenous (IV) PRL3-zumab reduced vascular leakage by 86 percent more than intravitreal (IVT) injections, enabling higher dosing and sustained retinal levels. Mechanisms involved inhibiting PRL3-mediated phosphorylation of ERK1/2, AKT, Paxillin, and SRC, curbing endothelial proliferation, migration, and permeability.

VEGF, a key driver, upregulated PRL3 in human retinal microvascular endothelial cells (HRMECs); PRL3 knockout abolished VEGF-induced proliferation. These findings position PRL3-zumab as a novel anti-angiogenic agent for non-responders.

The multidisciplinary team included experts from IMCB, highlighting Singapore's collaborative research ethos.

Researchers and Institutions Driving Innovation

Lead author Dr. Koon Hwee Ang and senior author Prof. Qi Zeng, an adjunct professor at NUS's Department of Biochemistry, spearheaded the effort. Co-authors hailed from Duke-NUS Medical School's Centre for Vision Research, Singapore Eye Research Institute (SERI), and NUS Yong Loo Lin School of Medicine's Ophthalmology Department.

A*STAR IMCB, with its 40-year legacy, fosters ties with NUS and NTU through joint labs and training. Prof. Zeng's dual role exemplifies how adjunct positions bridge public research and academia, mentoring PhD students and postdocs. Assoc. Prof. Xinyi Su, IMCB Executive Director and NUS ophthalmologist, emphasized clinician-scientist collaborations.

This ecosystem supports aspiring academics; explore opportunities at university-jobs in Singapore's top institutions.

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Overcoming Limitations of Existing Treatments

Anti-VEGF therapies revolutionized wet AMD/DME management but falter for many. In Singapore, frequent clinic visits burden patients, especially elderly diabetics.

• Monthly IVT injections risk endophthalmitis (1/1000), cataract, and dropout.
• 45 percent non-responders due to fibrosis or resistance.
• IVT limits dosing; systemic toxicity precludes IV use.

PRL3-zumab circumvents these: IV administration is painless, scalable, and achieves superior leakage reduction. Preclinical data showed prolonged efficacy, potentially reducing frequency.Read the full study.

Regulatory Milestone and Clinical Trial Roadmap

Singapore's Health Sciences Authority (HSA) approved a Phase I safety trial on June 16, 2025, enrolling 15 patients for IV PRL3-zumab in wet AMD/DME by late 2025. Building on cancer Phase II data, it prioritizes safety before efficacy trials.

Singapore's efficient regulation accelerates translation, contrasting longer timelines elsewhere. Success could fast-track Phase II/III, positioning Singapore as an ophthalmology trial hub.

Singapore's Higher Education Fueling Biotech Breakthroughs

NUS and Duke-NUS contributions underscore higher education's role. Prof. Zeng's adjunct status at NUS facilitates student training; Duke-NUS provides clinical insights via SERI. IMCB-NUS collaborations, including joint PhD programs, nurture talent.

Singapore invests heavily in RIE2025/RISE2030, funding biomedical clusters. This yields spin-offs like Intra-ImmuSG, creating jobs. For career advice, visit higher-ed-career-advice.

Stakeholder Perspectives and Broader Impacts

Dr. David Ang, inspired by his father's struggles, noted PRL3-zumab's pipe-fixing analogy for leakage. Prof. Zeng highlighted 20 years of safe targeting.

Clinicians anticipate better compliance; patients fewer visits. Economically, reduced injections could save millions, easing Singapore's aging demographic pressures.

Photo by CJ Dayrit on Unsplash

Future Outlook: Transforming Global Vision Care

If trials succeed, PRL3-zumab could redefine neovascular disease management worldwide, especially in Asia's diabetes surge. Singapore's model—integrated higher ed, research institutes, and startups—offers lessons for emerging biotech nations.

Researchers should monitor trial data; students pursue ophthalmology/biotech via scholarships. Rate professors shaping this field at rate-my-professor.

For jobs advancing such innovations, check higher-ed-jobs, university-jobs, and higher-ed-career-advice.