2. Academic Validation
  3. PRL3-zumab as an anti-angiogenic therapy in neovascular eye diseases

PRL3-zumab as an anti-angiogenic therapy in neovascular eye diseases

  • Nat Commun. 2025 May 23;16(1):4791. doi: 10.1038/s41467-025-59929-2.
Koon Hwee Ang 1,  Min Thura 1,  Queenie Shu Woon Tan 1,  Abhishek Gupta 1,  Kam Yew Kuan 1,  Jie Li 1,  Pei Ling Chia 1,  Beiying Qiu 2,  Jimmy Ming Hong 3,  Ke Guo 1,  Xiaomeng Wang 1 2 3,  Xinyi Su 1 3 4 5,  Qi Zeng 6 7
Affiliations

Affiliations

  • 1 Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Singapore, 138673, Singapore.
  • 2 Centre for Vision Research, Duke NUS Medical School, 8 College Road, Singapore, 169857, Singapore.
  • 3 Singapore Eye Research Institute (SERI), The Academia, 20 College Road, Level 6 Discovery Tower, Singapore, 169856, Singapore.
  • 4 Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119260, Singapore.
  • 5 Department of Ophthalmology, National University Hospital, Singapore, 119074, Singapore.
  • 6 Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Singapore, 138673, Singapore. mcbzengq@imcb.a-star.edu.sg.
  • 7 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119260, Singapore. mcbzengq@imcb.a-star.edu.sg.
PMID: 40410189 DOI: 10.1038/s41467-025-59929-2
Abstract

Neovascular eye diseases represent a major cause of irreversible blindness. Here, we report the specific upregulation of endogenous PRL3 protein in diseased choroid-RPE in choroidal neovascularization (CNV) mouse model (male), and diseased retina in oxygen-induced retinopathy (OIR) mouse model (mixed gender), indicating PRL3's role in neovascularization. Intravenous (IV) delivery of anti-PRL3 antibody in CNV model demonstrates superior efficacy in reducing vascular leakage compared to intravitreal (IVT) route due to larger dose permitted by IV. VEGF treatment upregulates endogenous PRL3 protein in human retinal microvascular endothelial cells (HRMECs). Retroviral PRL3 overexpression in HRMECs promotes endothelial proliferation, migration and permeability by facilitating the phosphorylation of ERK1/2, Akt, Paxillin and Src. However, VEGF-induced proliferation is absent in PRL3-knockout HRMECs. PRL3-zumab, an anti-PRL3 humanized monoclonal antibody, has shown a strong safety profile in ongoing multi-national Phase II trials as an intravenous-administered Cancer immunotherapeutic. PRL3's involvement in ocular pathological angiogenesis suggests the potential of repurposing PRL3-zumab to treat neovascular eye diseases.

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