Blood vessels are the highways of life, delivering oxygen and nutrients to our organs while removing waste. However, neovascular eye diseases such as wet age-related macular degeneration (AMD) and diabetic macular edema (DME) can wreak havoc on these highways by causing new blood vessels to sprout wildly—an effect known as angiogenesis. This chaotic tangle can leak fluid into the eyes, causing vision impairment or even blindness.
Existing drugs for these diseases all target the vascular endothelial growth factor (VEGF) protein, which triggers angiogenesis when overexpressed, explained Qi Zeng, a Research Director at the A*STAR Institute of Molecular and Cell Biology (A*STAR IMCB).
“However, around 40 percent of patients with neovascular eye diseases respond poorly to anti-VEGF therapies, yet there’s a lack of alternative options,” said Zeng. “These therapies also involve multiple invasive eye injections annually—which carry risks of eye injuries—and aren’t recommended for those with pre-existing cardiovascular issues due to safety concerns. Yet, these patient groups are often also the ones at higher risk of contracting neovascular eye diseases.”
In 2015, Zeng’s team had found that the PRL3 protein, which is involved in tumour angiogenesis, was also highly expressed in diseased eye tissues but not normal eye tissues. This preliminary observation sparked the idea that PRL3-zumab—a humanised PRL3-targeting antibody developed by the same team for suppressing tumours could also be repurposed for neovascular eye diseases.
To pursue this idea, Zeng teamed up with A*STAR IMCB colleagues including Senior Scientist Koon Hwee David Ang, Senior Scientist Min Thura, Executive Director Xinyi Su and Research Officer Queenie Tan; Xiaomeng Wang and colleagues at Duke-NUS Medical School; and A*STAR spinoff Intra-ImmuSG (IISG).
The researchers first confirmed that PRL3 was only overexpressed in diseased and not healthy eye tissue layers in mouse models of wet AMD and DME. They had previously established PRL3’s absence from multiple organs in mature humans, suggesting its safety and specificity as a drug target.
The researchers first confirmed that PRL3 was only overexpressed in diseased and not healthy eye tissue layers in mouse models of wet AMD and DME. They had previously established PRL3’s absence from multiple organs in mature humans, suggesting its safety and specificity as a drug target.
“The IV route mitigates the risks of IVT and allows the delivery of a larger dose of PRL3-zumab, which enters the eye through leaky blood vessels,” said Ang. “What’s more, the IV route keeps the drug in circulation, slowing the rate at which it dissipates from the eyes, which sustains high therapeutic levels thereof.“
Zeng added that to date, IV PRL3-zumab has also been trialled in over 220 patients in cancer clinical trials sponsored by IISG, providing established human safety data for its use in treating eye diseases.
At present, the team has successfully obtained regulatory approval from Singapore’s Health Sciences Authority for a Phase I/II clinical trial of PRL3-zumab in wet AMD. The trial is underway at the National University Hospital, and as of September 2025, is actively recruiting wet AMD patients who are resistant to anti-VEGF therapies.
The A*STAR-affiliated researchers contributing to this research are from the A*STAR Institute of Molecular and Cell Biology (A*STAR IMCB).
