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What Does VEGF Do in the Eye?

By: Kathryn Senior PhD - Updated: 28 Oct 2012 | comments*Discuss
Vascular Endothelial Growth Factor

The sense of sight is very precious because of the things that it enables us to do. It is also fragile. The tissues of the retina, which contains the photoreceptor cells that convert images that come into the eye from the outside world can never be regenerated once they are damaged. As we get older, various aging processes take place in the retina and these can cause swelling and inflammation, which can lead to vision loss very rapidly. Diseases such as age related macular degeneration, retinal vein occlusion and diabetic retinopathy are responsible for many cases of blindness in the over 60s. Glaucoma and eye injuries can also damage the retina.

One of the molecules in the eye that protects it from damage is, ironically, one of the main mediators of damage when something goes wrong. Vascular endothelial growth factor – known as VEGF for short – promotes healing in the normal eye and maintains good eyesight. When damage occurs, more is produced as the body tries to heal the problem, but this causes more swelling, more inflammation – and more damage.

Types of VEGF

There are several types of VEGF. In fact, this is a whole family of molecules and the different members have been name fairly unimaginatively. VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-E and VEGF-F. One other member is called placental growth factor (PGF) but this has no role to play in the eye. Some of the other VEGF molecules are only produced during a viral infection. The main VEGF type that is relevant to eye health is VEGF-A.

The Normal Function of VEFG-A in the Eye

VEGF is such a complex family of molecules that we are only just starting to tease apart all of the functions of each individual type. VEGF-A plays a vital role in the eye as it protects the nerves from damage and also helps to heal minor problems in the blood vessels that exist in a rich layer just underneath the retina. This layer is called the choroid and it contains thousands of tiny blood capillaries that deliver freshly oxygenated blood to the cells of the retinal, and then take away metabolic wastes and carbon dioxide. This process needs to be very efficient to keep the retina working at maximum efficiency.

The neuroprotective and vascular healing effects of VEGF-A in the eye were only discovered fairly recently.

Complications of Blocking VEFG-A

In retinal diseases, VEGF-A is over produced and causes swelling and also the growth of new blood vessels at the back of the retina. This happens to try to get more oxygen to retinal tissues that have been damaged – and to increase the number of white blood cells to the area to try to heal the tissue damage. The overall effect is to cause swelling in the retina, which disrupts the delicate layers and also to push into the retina with new blood vessels. These grow randomly and do not keep within the choroid. They can actually push through the retina, damaging photoreceptor cells that were previously OK, and then cause bleeding into the vitreous humour. This causes intense clouding, leading to severely blurred vision.

Blocking VEGF-A using drugs specifically developed for use in the eye can help slow down this process and these drugs – such as Lucentis – have shown very good results. The problem is that as well as blocking the harmful effect of VEGF-A, they also stop the molecule being able to carry out the normal neuroprotective and vascular healing processes.

New Drugs for Retinal Disease

Some of the newer drugs that block the action of VEGF-A only block the specific sub-types of the molecule that cause damage rather than heal the eye tissues. One drug, Macugen, is very specific for only one subtype of VEGF-A –the one responsible for most of the damage. It hasn’t yet been approved for eye disease but researchers are hoping that it will have the same effect as Lucentis, but without the long term effects on normal eye healing.

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