Researchers at UCL have identified a protein called LRG1 that initiates the earliest damage in diabetic retinopathy, a major cause of vision loss in adults with diabetes. In mouse studies, blocking LRG1 prevented retinal harm and preserved eye function. The findings suggest potential for new preventive treatments targeting this protein.
Diabetic retinopathy, which damages the retina's blood vessels due to high blood sugar, is a leading cause of vision loss among working-age adults. A study led by scientists at the UCL Institute of Ophthalmology reveals that the protein LRG1 plays a crucial role in starting this damage early on.
Published in Science Translational Medicine, the research used diabetic mouse models to show how LRG1 causes pericytes—cells around the eye's smallest blood vessels—to constrict them excessively. This reduces oxygen supply to the retina, sparking a process that can lead to long-term vision problems.
When researchers blocked LRG1 in these mice, early retinal damage did not develop, and normal eye function was maintained. The work was supported by Diabetes UK, Moorfields Eye Charity, and Wellcome.
Lead author Dr. Giulia De Rossi stated: "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."
Current treatments, which target the protein VEGF, help only about half of patients and cannot reverse existing damage. LRG1 appears to drive harm earlier than VEGF, offering a new therapeutic target. The UCL team has developed a drug to block LRG1, which has undergone initial testing and is in further preclinical stages, with possible human trials ahead.
This builds on years of UCL research into LRG1's role in eye diseases. In 2019, co-authors Professors John Greenwood and Stephen Moss co-founded Senya Therapeutics to advance LRG1-targeting drugs.
Professor John Greenwood noted: "This study delivers vital insight into the disease and shows that therapeutic targeting of LRG1 has real clinical potential." Professor Emeritus Stephen Moss added: "The good news to accompany these findings is that we have already developed an LRG1 therapeutic ready for clinical trials."
Dr. Faye Riley from 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."
The discovery affects both type 1 and type 2 diabetes patients and could prevent retinopathy from starting or progressing.
