Related Experiment Video
Updated: Jan 14, 2026
Retinal Explant of the Adult Mouse Retina as an Ex Vivo Model for Studying Retinal Neurovascular Diseases
Published on: December 9, 2022
Erdafitinib suppresses pathological retinal angiogenesis via dual targeting of FGFR and VEGFR2 signaling
Yingli Mo1,2, Bei Lu1, Yuping Xu3
1Hunan Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China.
Abstract:
Pathological retinal angiogenesis drives vision loss in diseases like proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO). Erdafitinib, a pan-fibroblast growth factor receptor (FGFR) inhibitor, has shown therapeutic potential in FGFR-mutated urothelial carcinoma. This study aimed to determine whether erdafitinib suppresses pathological retinal angiogenesis beyond its canonical FGFR inhibition, and to dissect its potential mechanisms through multi-model validation. We employed zebrafish developmental angiogenesis and oxygen-induced retinopathy (OIR) mouse models, combined with in vitro endothelial cell assays. In zebrafish, erdafitinib dose-dependently inhibited intersegmental vessel (ISV) formation and disrupted retinal angiogenesis, with confocal microscopy revealing truncated vascular length (by 62% at 4 µM vs. controls). The OIR model demonstrated erdafitinib's efficacy in reducing neovascular density (35% decrease) and pathological tuft formation. Mechanistically, erdafitinib impaired human umbilical vein endothelial cell (HUVEC) tube formation and migration, accompanied by downregulation of VEGFR2 expression (2.1-fold reduction) and inhibition of AKT/ERK phosphorylation. Molecular docking confirmed erdafitinib's binding to VEGFR2 kinase domain (binding energy: -7.8 kcal/mol), albeit with lower affinity than FGFR1 (-10.2 kcal/mol). These findings establish that erdafitinib exerts off-target anti-angiogenic effects by blocking VEGFR2 phosphorylation and downstream signaling, supporting its repurposing potential for anti-VEGF-resistant retinal vascular diseases. Further studies should address its intraocular pharmacokinetics and long-term safety.
Insights
Erdafitinib, an FGFR inhibitor, shows potential for treating retinal diseases by inhibiting pathological angiogenesis. It effectively reduces blood vessel growth by blocking VEGFR2 signaling, offering hope for conditions resistant to anti-VEGF therapies.
Area of Science:
- Ophthalmology
- Pharmacology
- Molecular Biology
Background:
- Pathological retinal angiogenesis causes vision loss in diseases like proliferative diabetic retinopathy (PDR) and retinal vein occlusion (RVO).
- Erdafitinib is a pan-fibroblast growth factor receptor (FGFR) inhibitor with demonstrated efficacy in FGFR-mutated urothelial carcinoma.
Purpose of the Study:
- To investigate erdafitinib's anti-angiogenic effects in retinal diseases beyond its known FGFR inhibition.
- To elucidate the underlying mechanisms of erdafitinib's action in suppressing pathological retinal angiogenesis.
Main Methods:
- Utilized zebrafish developmental angiogenesis and oxygen-induced retinopathy (OIR) mouse models.
- Conducted in vitro human umbilical vein endothelial cell (HUVEC) assays.
- Performed molecular docking to assess erdafitinib's binding to VEGFR2 and FGFR1.
Main Results:
- Erdafitinib dose-dependently inhibited zebrafish vascular development and reduced neovascularization in the OIR mouse model.
- Erdafitinib impaired HUVEC tube formation and migration, downregulating VEGFR2 expression and inhibiting AKT/ERK phosphorylation.
- Molecular docking indicated erdafitinib binds to VEGFR2 kinase domain, suggesting an off-target mechanism.
Conclusions:
- Erdafitinib exhibits anti-angiogenic properties by inhibiting VEGFR2 phosphorylation and downstream signaling pathways.
- These findings support the potential repurposing of erdafitinib for retinal vascular diseases, particularly those resistant to anti-VEGF treatments.
- Further research is warranted on erdafitinib's intraocular pharmacokinetics and long-term safety profile.
