Potentiation of anti-VEGF effect by heparins: role in inhibiting angiogenesis in eye diseases

Abstract

Angiogenesis is the formation of new blood vessels from existing vessels, which occurs in several pathological processes such as choroidal neovascularization secondary to age-related macular degeneration (AMD), one of the main causes of irreversible low vision in the elderly, in the form of wet. Neovascularization is controlled by a complex interaction of pro-angiogenic and anti-angiogenic factors, and the most studied pro-angiogenic regulatory molecule in this process is vascular endothelial growth factor (VEGF), which plays an important role in the survival, proliferation, and migration of endothelial cells. The treatment of wet AMD currently consists of intravitreal injections of anti-VEGF drugs (Bevacizumab, Ranibizumab, or Aflibercept) which are expensive, not fully effective, and need to be administered with high frequency. So, the search for emerging therapies that improve treatment efficacy, and decrease the cost/frequency of injections is highly relevant to treat this ocular neovascularization. Our laboratory has been working for a long time with the anti-angiogenic activity of heparins and heparinoids, as heparin also has the ability to bind and modulate the activity of VEGF and other angiogenic factors. In this context, the objective of this study is to evaluate the antiangiogenic potential of 6-O-desulfated heparin (HepM), chemically modified in our laboratory, and the possible potentiation of the anti-angiogenic action of the HepM-bevacizumab complex for the development of a new treatment.(AU)