Diabetic Retinopathy: A Variant Of A Growth Factor Responsible For Abnormal Blood Vessel Growth And Eye Damages

A variant form of a common growth factor, called VEGF (vascular endothelial growth factor) was identified that is responsible for the inflammation and altered retinal vascularisation that occurs in diseases such as diabetic retinopathy (DR). It could become the target for novel therapies that will help to solve, or at least to ease, a pathology which is poorly treatable by common drugs. The announcement was made yesterday by Professor David T. Shima, Group Leader at the University College of London, Institute of Ophthalmology, at the European Meeting on Vascular Biology and Medicine, held in parallel with the Fourth Annual Meeting of EVGN (www.evgn.org), network of excellence on cardiovascular disease.

Diabetic retinopathy is a leading cause of blindness and is characterized by the invasive growth and abnormal function of blood vessels within the retina, that obstructs vision and triggers other unwanted effects. With an estimate of 500.000 new cases of severe disease per year in Western Countries it is rightly considered a sanitary priority. Many research groups are focussing on potential targets, but so far no effective pharmacological approaches have been proven to substitute the current (destructive) surgical therapies.

David T. Shima and colleagues focused on a growth factor known to be produced during ischemic conditions, when the eye suffers from lack of oxygen. VEGF, this is its name, counterbalances this condition by promoting blood vessel growth. In diabetic retinopathy VEGF is part of an adaptive response to ischemia, that unfortunately in the long run becomes noxious per se.

“We observed – explained the scientist – that, blood vessels in the ischemic retina do regrow but in a disorganized way: they form clumps instead of a fine mesh-like network. UK scientists asked why and clarified the role of VEGF.

“We decided to further characterize the VEGF activity responsible for the abnormal response and identified one alternative form (or isoform) called VEGF 164, that drives not only ocular neovascularization and vascular permeability, but also an undesirable inflammatory reaction. When this form is genetically or pharmaceutically inhibited the pathological neovascularization is inhibited as well, and blood vessels sprout normally”. Further analysis spotted a specific region within this molecule that is the major cause of inflammation, another characteristic of DR. Again, mutations in this region abolish the undesired pro-inflammatory effects

“Certainly, the inflammatory function of VEGF 164 represents a promising target for the treatment of diabetic retinopathy. However there is one problem to solve: VEGF has a second, beneficial role as it protects neurons from ischemic death. Its complete elimination would trigger unwanted consequences and further research is needed to understand this apparent contradiction. Better understanding of the risks and benefits could pave the way for the treatment of this sight-threatening human disease”.

Run jointly with the European Vascular Biology Organization (EVBO) and the British Atherosclerosis Society and articulated over a three day period (September 17-20), the EVGN Meeting will take place in parallel with the 4th European Meeting on Vascular Biology and Medicine (EMVBM), gathering more than 400 scientists from all over Europe with representatives from the rest of the world.

The European Vascular Genomics Network (EVGN) is the first Network of excellence on cardiovascular disease funded by the European Commission under the 6th Framework Programme “Life sciences, genomics and biotechnology for health” (Contract Number: LSHMCT- 2003-503254).

The Conference is supported by an unrestricted educational grant from Laboratoires SERVIER.