Protein Discovery Offers New Hope in Preventing Diabetic Blindness

Researchers have identified a protein, leucine-rich α-2-glycoprotein 1 (LRG1), as a key trigger of early retinal damage in diabetic retinopathy, a leading cause of vision loss for people with diabetes. Blocking this protein in preclinical studies halted early retinal injury and preserved eye function, suggesting a potential new approach to preventing diabetic blindness before symptoms develop.

Early Detection and Limitations of Current Treatments

Diabetic retinopathy affects individuals with both type 1 and type 2 diabetes and can lead to blurred or distorted vision. Current treatments primarily target vascular endothelial growth factor A (VEGF), a protein that regulates blood vessel growth. However, these therapies are effective for only approximately 50% of patients and often fail to reverse existing damage.

The new research indicates that LRG1 initiates eye damage earlier in the disease process than VEGF, the current therapeutic target. This discovery suggests that intervening at the LRG1 stage could offer a more effective preventative strategy.

“Nearly a third of adults with diabetes have some signs of retinopathy, and it is one of the most feared complications of the condition,” said Dr. Faye Riley, research communications lead at Diabetes UK, which part-funded the research. “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.”

How LRG1 Causes Early Retinal Damage

The researchers found that LRG1, involved in cellular signaling, causes the cells surrounding the eye’s smallest blood vessels to constrict excessively, effectively ‘squeezing’ them. This constriction reduces oxygen delivery to the retina, potentially leading to long-term visual impairment.

In experiments using mouse models of diabetes, blocking LRG1 activity prevented early retinal damage and preserved normal eye function.

“Our discovery shows that diabetic eye disease starts earlier than we thought, and LRG1 is a key culprit in this early damage,” explained Dr. Giulia De Rossi (UCL Institute of Ophthalmology), the lead author of the study. “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.”

UCL Develops LRG1-Blocking Drug

Researchers at University College London (UCL) have developed a drug designed to block LRG1. The therapy is currently undergoing preclinical research and early testing. The team believes this approach could prevent the development of diabetic retinopathy altogether.

This research builds upon years of investigation at the UCL Institute of Ophthalmology into the role of LRG1 in eye disease.

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

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.”

Dr. Ailish Murray, director of grants and research at Moorfields Eye Charity, stated, “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.”