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Aflibercept Action in a Rabbit Model of Chronic Retinal Neovascularization: Reversible Inhibition of Pathologic

Jingtai Cao1, Thomas C MacPherson1, Bibiana V Iglesias1

  • 1Regeneron Pharmaceuticals, Inc., Tarrytown, New York, United States.

Investigative Ophthalmology & Visual Science
|February 17, 2018
PubMed
Abstract

Insights

Intravitreal aflibercept effectively blocked leakage in a chronic retinal neovascularization rabbit model. The anti-leak effect was reversible, lasting about 8 weeks, and partially regressed abnormal vasculature.

Area of Science:

  • Ophthalmology
  • Retinal Vascular Diseases
  • Pharmacology

Background:

  • Chronic retinal neovascularization (RNV) is a significant cause of vision loss.
  • Existing models may not fully replicate the stability and persistence of human RNV.
  • Understanding the long-term effects of anti-angiogenic therapies is crucial.

Purpose of the Study:

  • To establish and characterize a chronic RNV rabbit model using intravitreal (IVT) DL-α-aminoadipic acid (AAA).
  • To investigate the inhibitory effects and duration of IVT aflibercept on established RNV in this model.
  • To assess the reversibility and dose-dependency of aflibercept's anti-leak action.

Main Methods:

  • Induction of chronic RNV in rabbits via single IVT AAA injection.
  • Weekly monitoring using fundus photography, fluorescein angiography (FA), and optical coherence tomography (OCT).
  • Administration of IVT aflibercept or control injection at 10 weeks, followed by leakage quantification and histological analysis.

Main Results:

  • IVT AAA successfully induced stable RNV with persistent leakage for over 65 weeks.
  • IVT aflibercept completely blocked RNV leakage, with effects lasting approximately 8 weeks for 500 μg.
  • Aflibercept demonstrated reversible anti-leak effects and induced partial regression of pathologic vasculature.

Conclusions:

  • The AAA-induced RNV rabbit model accurately mimics chronic human retinal vascular diseases.
  • Aflibercept's anti-leak action is fully reversible and exhibits dose-dependent duration.
  • This model is valuable for studying novel pharmacotherapies and the pathobiology of retinal angiogenesis.

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