UCL Researchers Identify LRG1 Protein as Early Trigger of Diabetic Retinopathy

Researchers led by scientists at UCL have discovered a protein that appears to set off diabetic retinopathy, a common eye disease caused by high blood sugar damaging the retina's blood vessels. The condition is one of the leading causes of vision loss among working-age adults. The study, conducted in mice and supported by Diabetes UK, Moorfields Eye Charity and Wellcome, could change how doctors approach the disease.

The findings, published in Science Translational Medicine on March 7, 2026, 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 the discovery shows that diabetic eye disease starts earlier than previously thought, and LRG1 is a key culprit in this early damage.

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.

Nearly a third of adults with diabetes have some signs of retinopathy, and it is one of the most feared complications of the condition. The research communications lead at Diabetes UK, who part funded the research, commented that 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.

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 the 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 that an LRG1 therapeutic ready for clinical trials has already been developed, which could provide an effective new option for patients, especially those in the early stages of disease who don't respond to existing treatments.