Early trigger of diabetic eye disease identified

A team led by UCL scientists has identified a key protein that triggers diabetic retinopathy—a condition caused by high blood sugar damaging the retina’s blood vessels and a leading cause of sight loss among working-age adults.

The research in mice has the potential to revolutionize how the disease is treated, shifting the treatment from managing late-stage damage to preventing vision loss before it begins.

The findings, published in Science Translational Medicine, reveal that a protein called LRG1 plays a critical role in initiating the earliest stage of retinal damage after diabetes develops. LRG1 causes the cells that wrap around the eye’s smallest blood vessels to constrict excessively and “squeeze” them, reducing oxygen supply to the retina and laying the groundwork for long-term visual impairment.

Importantly, when researchers blocked LRG1 activity in mouse models of diabetes, they were able to prevent this early damage and preserve healthy eye function.

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.”

Diabetic retinopathy affects people with both type 1 and type 2 diabetes. It is typically only treated once symptoms—such as blurred or distorted vision—appear, by which point irreversible damage has already occurred. Even then, current therapies—which target another protein, VEGF—only work for around 50% of patients and rarely reverse existing harm in an impactful way.

This new research shows that LRG1 starts causing eye damage far earlier than VEGF, making it a promising new therapeutic target. Unlike current treatments, a treatment that blocks LRG1 could intervene before vision deteriorates and prevent disease progression altogether.

Dr. Faye Riley, research communications lead at Diabetes UK, 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-based researchers have already developed a tried and tested LRG1-targeting drug, which is currently undergoing further pre-clinical studies and could be ready for clinical trials in humans in the near future. The researchers believe this therapy will not only halt the onset of diabetic retinopathy but can also be effective in later stage disease where LRG1 continues to play a role.

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.”