The study, conducted in mice and supported by Diabetes UK, Moorfields Eye Charity and Wellcome, could change how doctors approach the disease. Instead of treating damage after it has already occurred, future therapies may be able to stop vision loss before it begins.

Protein LRG1 Linked to Early Retinal Damage

The findings, published in Science Translational Medicine, point to a protein called LRG1 as a key factor that triggers the earliest stage of retinal damage after diabetes develops.

Researchers found that LRG1 causes cells surrounding the eye’s tiniest blood vessels to tighten excessively and ‘squeeze’ them. This constriction reduces oxygen delivery to the retina and begins a chain reaction that can eventually lead to long term vision impairment.

In experiments using diabetic mouse models, scientists were able to block the activity of LRG1. When they did so, the early retinal damage did not occur and normal eye function was preserved.

Lead author Dr. Giulia De Rossi (UCL Institute of Ophthalmology) said: “Our discovery shows that diabetic eye disease starts earlier than we thought, and LRG1 is a key culprit in this early damage. Targeting this protein could give us a way to protect vision before serious damage occurs and prevent, rather than treat, blindness in millions of people living with diabetes.”

Why Current Treatments Are Limited

Diabetic retinopathy affects people with both type 1 and type 2 diabetes. In many cases, treatment only begins once symptoms such as blurred or distorted vision appear. By that point, significant and irreversible damage may already have occurred.

Existing treatments focus on another protein called VEGF. However, these therapies work for only about half of patients and typically do not reverse the harm that has already developed.

The new research suggests that LRG1 begins driving eye damage much earlier than VEGF. Because of this, scientists believe it may represent a promising new target for therapy. A treatment designed to block LRG1 could potentially intervene earlier and stop the disease from progressing.

Potential New Treatment for Diabetic Eye Disease

Dr. Faye Riley, research communications lead at Diabetes UK who part funded the research, commented: “Nearly a third of adults with diabetes have some signs of retinopathy, and it is one of the most feared complications of the condition. By identifying the root cause of early damage, and offering a new path for treatment, this research holds immense promise for protecting the sight of the growing number of people with diabetes worldwide.”

The UCL research team has already created a drug designed to target LRG1. The treatment has been tested in earlier studies and is currently undergoing additional preclinical research. Scientists say it could move into human clinical trials in the near future.

Researchers believe the therapy could help prevent diabetic retinopathy from developing in the first place. It may also benefit people with more advanced disease because LRG1 continues to contribute to damage at later stages.

Years of Research Behind the Discovery

The new findings build on several years of research by scientists at the UCL Institute of Ophthalmology investigating how LRG1 contributes to eye disease.

Co authors Professors John Greenwood and Stephen Moss were among the first to identify the role of LRG1 in ocular disease. In 2019 they founded Senya Therapeutics, a UCL spinout company created with the support of UCL Business to develop drugs that target LRG1.

Co author Professor John Greenwood (UCL Institute of Ophthalmology), world expert in LRG1 biology, said: “This study delivers vital insight into the disease and shows that therapeutic targeting of LRG1 has real clinical potential. The discovery that LRG1 is an early initiating factor driving diabetic retinopathy is enormously exciting.”

Co author Professor Emeritus Stephen Moss (UCL Institute of Ophthalmology) added: “The good news to accompany these findings is that we have already developed an LRG1 therapeutic ready for clinical trials. This could provide an effective new option for patients, especially those in the early stages of disease who don’t respond to existing treatments.”

Hope for Protecting Vision in People With Diabetes

Dr. Ailish Murray, director of grants and research at Moorfields Eye Charity, said: “The early stages of diabetic retinopathy are often difficult to detect, leaving many people with irreversible damage once the symptoms have occurred. This research offers an important and vital next step in helping to prevent this disease, offering the chance to save the sight of millions of people living with diabetes now and in the future.”

Morag Foreman, head of discovery researchers at Wellcome, said: “This is an exciting breakthrough, lighting a potential path towards treatment for diabetic eye disease. These findings are a result of cutting-edge discovery research and demonstrate the importance of backing early science that could translate to meaningful advances in medicine.”