Language
English
Publication Date
2-1-2026
Journal
Geroscience
DOI
10.1007/s11357-025-01732-4
PMID
40518488
PMCID
PMC12972489
PubMedCentral® Posted Date
6-15-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Recent studies reported that anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF) alleviate choroidal neovascularization (CNV) in young but not aged animals. We recently developed a disease-targeted anti-angiogenic therapy against secretogranin III (Scg3), which selectively binds to diseased but not healthy vessels in young mice. Herein, using a unique in vivo ligand binding assay, we predicted and confirmed that Scg3 selectively binds CNV vessels in both young and aged mice. In contrast, VEGF with minimal increased binding to CNV vessels exhibited an age-dependent decline in binding to both CNV and healthy vessels with negligible binding in aged mice. Based on these binding activity patterns, we further predicted and confirmed that a humanized anti-Scg3 antibody effectively alleviated laser-induced CNV in both young and aged mice, whereas the anti-VEGF drug aflibercept was effective only in young mice. These findings suggest that enhanced binding of Scg3 to CNV vessels in both age groups provides a molecular basis for an age-independent anti-Scg3 therapy, offering potential to address anti-VEGF resistance in clinical treatment of wet age-related macular degeneration with CNV.
Keywords
Animals, Choroidal Neovascularization, Mice, Angiogenesis Inhibitors, Chromogranins, Disease Models, Animal, Mice, Inbred C57BL, Vascular Endothelial Growth Factor A, Recombinant Fusion Proteins, Receptors, Vascular Endothelial Growth Factor, Vascular endothelial factor, Secretogranin III, Scg3, Anti-angiogenic therapy, Choroidal neovascularization, Age-related macular degeneration
Published Open-Access
yes
Recommended Citation
Chengchi Huang, Hong Tian, and Wei Li, "Age-Independent Anti-Angiogenic Therapy for Choroidal Neovascularization by Targeting Secretogranin III" (2026). Faculty, Staff and Students Publications. 7407.
https://digitalcommons.library.tmc.edu/baylor_docs/7407