Research Topics

Endothelial cell differentiation during angiogenesis

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.

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Active HIF-1 in the normal human retina

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.

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Blood-retinal barrier (BRB) loss is crucial in the pathogenesis of diabetic retinopathy. In preclinical diabetic retinopathy it occurs early as diffuse retinal vascular permeability and may represent an important mechanism accelerating the early retinal changes caused by diabetes.

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Connective tissue growth factor (CTGF) plays an important role in the development of different stages of DR.

The Angio-Fibrotic Switch

The TGF-β superfamily of GFs, which includes TGF-βs and bone morphogenetic proteins (BMPs) has important cell- and context-dependent functions in the regulation of extracellular matrix turnover, fibrosis and angiogenesis, but evidence for involvement of these GFs in DR is inconclusive. Recently, the signalling pathways of these GFs were defined, and specifically in endothelial cells, two distinct pathways were discovered that allow pro- or anti-angiogenic signalling by TGF-β through its receptors ALK1 and ALK5. In other cell types, the balance between TGF-β and BMP signalling regulates fibrosis.

Up-regulated basolateral VEGF secretion by RPE in hypoxia or loss of polarity of VEGF production may play a role in the pathogenesis of choroidal neovascularization.

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