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Updated: Mar 21, 2026
Retinal Explant of the Adult Mouse Retina as an Ex Vivo Model for Studying Retinal Neurovascular Diseases
Published on: December 9, 2022
An APE1 Redox Inhibitor Attenuates Pathological Retinal Vascularization by Suppressing FGF2 Angiogenic Signaling
Chenfei Yan1, Qiangqiang Fu2, Jiawei Wang1
1Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, People's Republic of China.
Purpose:
Retinal neovascular (RNVs) diseases are major causes of visual loss. Current first-line therapies for RNV primarily target VEGF. However, intrinsic or acquired resistance to anti-VEGF therapy, along with the risks associated with repeated intraocular injections, underscores the need for alternative targets and new therapeutic strategies. Apurinic/apyrimidinic endonuclease 1 (APE1) regulates transcription factors implicated in RNV. The purpose of this study was to evaluate APE1 as a therapeutic target, assess the potential of its redox inhibitor, Refi-10, as a drug candidate for vascular retinopathies, and elucidate underlying mechanisms.
Methods:
An oxygen-induced retinopathy (OIR) mouse model and the APE1 redox inhibitor Refi-10 were used to investigate the contribution of APE1 redox function in retinopathy neovascularization and assess the therapeutic efficacy of Refi-10. Transcriptomic analysis of OIR retinas identified pro-angiogenic factors and pathways associated with RNV and Refi-10-mediated improvement. Retinal pigment epithelium (RPE) and human retinal microvascular endothelial cells (hRMECs) were used to investigate cellular mechanisms and responses to Refi-10.
Results:
Refi-10 significantly reduced pathological angiogenesis and ameliorated RNV disease. Mechanistic studies showed that Refi-10 attenuated inflammation and angiogenesis via APE1 inhibition. Notably, Refi-10 did not decrease retinal VEGF in OIR but mitigated RNV by suppressing fibroblast growth factor 2 (FGF2) expression.
Conclusions:
These findings nominate APE1 and FGF2 signaling as promising therapeutic targets, and show that Refi-10 holds potential as a drug candidate for vascular retinopathies, offering an alternative or complementary approach to VEGF inhibition.
Insights
A new study shows that inhibiting Apurinic/apyrimidinic endonuclease 1 (APE1) with Refi-10 can treat retinal neovascular (RNV) diseases. This approach targets fibroblast growth factor 2 (FGF2) and offers an alternative to anti-VEGF therapies.
Area of Science:
- Ophthalmology
- Molecular Biology
- Pharmacology
Background:
- Retinal neovascular (RNV) diseases cause significant vision loss.
- Current anti-VEGF therapies face resistance and require frequent injections.
- Apurinic/apyrimidinic endonuclease 1 (APE1) is involved in RNV pathogenesis.
Purpose of the Study:
- To evaluate APE1 as a therapeutic target for RNV.
- To assess the efficacy of the APE1 redox inhibitor Refi-10 for vascular retinopathies.
- To elucidate the mechanisms underlying Refi-10's action in RNV.
Main Methods:
- An oxygen-induced retinopathy (OIR) mouse model was used.
- Refi-10's therapeutic efficacy and mechanisms were investigated.
- Transcriptomic analysis and cellular studies in RPE and hRMECs were performed.
Main Results:
- Refi-10 significantly reduced pathological angiogenesis and ameliorated RNV.
- Refi-10 attenuated inflammation and angiogenesis by inhibiting APE1.
- Refi-10 mitigated RNV by suppressing fibroblast growth factor 2 (FGF2) without affecting VEGF.
Conclusions:
- APE1 and FGF2 signaling are promising therapeutic targets for RNV.
- Refi-10 demonstrates potential as a drug candidate for vascular retinopathies.
- Refi-10 offers a complementary or alternative strategy to VEGF inhibition.
