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Synergistic Suppression of Choroidal Neovascularization by Cavtratin and Aflibercept via Inhibition of the eNOS

Yue Dong1, Yanlin Li2, Xuan Zhou1

  • 1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology Visual Science, Guangzhou, China.

Current Eye Research
|August 4, 2025
PubMed
Abstract

Insights

This study shows that Cavtratin combined with Aflibercept effectively treats choroidal neovascularization (CNV) by reducing inflammation and enhancing anti-angiogenic effects. This novel combination therapy offers a promising strategy to overcome resistance to anti-VEGF treatments for age-related macular degeneration.

Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Pharmacology

Background:

  • Choroidal neovascularization (CNV) is a primary cause of vision loss in exudative age-related macular degeneration (AMD).
  • Current anti-vascular endothelial growth factor (anti-VEGF) therapies face challenges like treatment insensitivity and drug resistance.
  • Caveolin-1 (Cav-1) plays a role in CNV pathogenesis.

Purpose of the Study:

  • To investigate the role of Caveolin-1 (Cav-1) in CNV.
  • To evaluate the therapeutic potential of Cavtratin, a Cav-1 scaffolding domain-targeting peptide.
  • To assess Cavtratin in combination with Aflibercept for CNV treatment.

Main Methods:

  • Utilized a laser-induced CNV mouse model and VEGF-stimulated human umbilical vein endothelial cells (HUVECs).
  • Assessed Cav-1 expression dynamics and its interaction with endothelial nitric oxide synthase (eNOS).
  • Evaluated Cavtratin's effects on angiogenesis via tube formation, choroidal sprouting, and fluorescein angiography; analyzed molecular changes and inflammation.

Main Results:

  • Cav-1 and eNOS were significantly upregulated in CNV progression.
  • Cavtratin inhibited angiogenesis and reduced CNV leakage, suppressing eNOS phosphorylation.
  • Combination therapy with Aflibercept demonstrated enhanced CNV inhibition, reduced inflammation, and allowed for lower Aflibercept dosage.

Conclusions:

  • Cavtratin combined with Aflibercept enhances anti-angiogenic efficacy and reduces inflammation in CNV.
  • Targeting the Cav-1/eNOS axis with Cavtratin offers a novel strategy to address limitations of anti-VEGF therapy.
  • Synergistic effects suggest a promising approach for overcoming treatment resistance in CNV management.
Keywords:
Choroidal neovascularization (CNV)anti-VEGF therapy resistancecaveolin-1 (Cav-1)cavtratinendothelial nitric oxide synthase (eNOS)

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