Academic Medical Center
Amsterdam
The Netherlands
Amsterdam
The Netherlands
The observations presented in this study, set against the background of existing literature on VEGF and CTGF, prompt us to propose a novel concept of the regulation of angiogenesis and fibrosis in ocular disease, and in wound healing in general. In this concept, angiogenesis in the vitreous is driven by VEGF, which amongst other factors upregulates the pro-fibrotic factor CTGF in various cell types in the newly formed neovascular membranes. Increasing levels of CTGF inactivate VEGF by reduction of production and complex formation, and when the equilibrium between these two factors shifts to a certain threshold ratio, the angio-fibrotic switch occurs and fibrosis driven by excess CTGF leads to scarring and blindness. This concept identifies CTGF as a major potential therapeutic target in the treatment of ocular fibrosis, in particular in combination with anti-VEGF agents.
This project aims to identify molecular mechanisms that regulate these different EC phenotypes, and to investigate the role of tip cell specific genes in regulating ocular angiogenic processes.
We provide evidence that HIF-1 signaling is constitutively active in the normal human retina. The retina is distinct from other tissues by the presence of photoreceptors which require enormous amounts of oxygen. The present study indicates that this causes not only physiological hypoxia, but also hypoxic molecular signaling via HIF-1alpha. These are unique features when compared to other normal tissues.
