Glycosylation of VEGF Receptors as Pathogenic Regulator of Retinopathies

Brief Lay background

The blood supply to the retina – the light-sensitive tissue at the back of the eye – is critically important for ensuring it receives the oxygen and nutrients needed to remain healthy.

Patients with certain eye conditions – including diabetic retinopathy, which is the most common cause of vision loss for people with diabetes – and wet age-related macular degeneration (wet AMD), can lose their central vision when abnormal blood vessels grow and leak under the retina.

Treatment with anti-VEGF drugs – which block the activity of a molecule called vascular endothelial growth factor (VEGF) – can help to stop abnormal blood vessel growth and leakage – helping to preserve central vision in many people with retinal blood vessel disorders.

What problem/knowledge gap does it help address

However, anti-VEGF drugs are only effective for around half of patients with retinal blood vessel disorders, which means that other factors must be involved in driving their disease.

The team has recently identified a molecule called Galectin-1 as another factor that could help drive blood vessel dysfunction in the retina – in addition to, or instead of, VEGF. But it appears that Galectin-1 can only act in this way when the blood vessels are modified with carbohydrate chains called glycans.

This suggests that Galectin-1 needs to be at increased levels in the retina – and there also needs to be a change of glycan fingerprint within the blood vessels – to cause disease.

Aim of the project

To establish if and how Galectin-1 contributes to retinal blood vessel disorders.

Key procedures/objectives

The researchers will carry out a series of experiments in mouse models of retinal disease, cell culture models of the cells that line the blood vessels, as well as donated human retinas to: 

1. Study changes to the glycan fingerprint within the blood vessels in the diseased retina.
2. Determine whether disease-causing glycan fingerprints can help promote the binding of Galectin-1 to blood vessels – and if this helps to drive the development and progression of retinal disease.
3. Test if it is possible to interfere with the formation of disease-causing glycan fingerprints – and if a drug already used to treat retinopathies (called aflibercept) also has the potential to block the activity of Galectin-1. 

Potential impact on people with sight loss

This research could ultimately pave the way for the development of effective new treatments for patients with retinal blood disorders who do not currently benefit from anti-VEGF drugs. This could help reduce sight loss for people affected by these conditions, dramatically improving their quality of life.