Scientists at University College London (UCL) have uncovered the "root cause" behind early diabetic blindness, identifying a key protein called LRG1 that triggers diabetic retinopathy—the leading cause of vision loss among working-age adults. This breakthrough could reshape treatment strategies, shifting focus from repairing damage after it occurs to preventing it at the earliest stages.
In a study published in Science Translational Medicine, the UCL team revealed that LRG1 plays a crucial role in initiating retinal injury in diabetes. High blood sugar levels cause LRG1 to prompt the cells surrounding the retina's smallest blood vessels to tighten, restricting oxygen flow to the retina and setting the stage for long-term vision problems.
When the researchers blocked LRG1 in diabetic mouse models, they were able to halt this early damage, preventing the progression of diabetic retinopathy and preserving normal eye function.
Dr. Giulia De Rossi, lead author of the study from UCL’s Institute of Ophthalmology, said, “Our discovery shows that diabetic eye disease starts earlier than previously thought. LRG1 is a key player in the early damage, and targeting it could allow us to protect vision before serious damage occurs, potentially preventing blindness in millions of people with diabetes.”
Currently, diabetic retinopathy is treated only after symptoms appear, such as blurred or distorted vision—often when the underlying damage is already permanent. Existing therapies, which target another protein called VEGF, benefit only around half of patients and rarely restore lost vision. However, LRG1 triggers eye damage much earlier than VEGF, making it a promising new target for early intervention.
Dr. Faye Riley, Research Communications Lead at Diabetes UK, noted, “Nearly a third of adults with diabetes show signs of retinopathy, making it one of the most feared complications of the condition. This research, which identifies the root cause of early damage, offers an exciting new avenue for protecting sight and could make a real difference to the growing number of people living with diabetes.”
The researchers have already developed a drug that targets LRG1, which is undergoing pre-clinical studies. The team hopes to begin clinical trials in humans soon, and they believe this therapy could be effective not only in preventing the onset of diabetic retinopathy but also in treating later stages of the disease where LRG1 continues to play a role.
This breakthrough is the culmination of years of research into the role of LRG1 in eye disease, led by UCL’s Professors John Greenwood and Stephen Moss, who previously identified LRG1’s involvement in ocular conditions. In 2019, they founded Senya Therapeutics, a UCL spinout, to develop LRG1-targeting drugs with the support of UCL Business.
Prof. John Greenwood, a world expert in LRG1 biology, said, “This study provides vital insights into the disease and shows the real clinical potential of targeting LRG1. It’s tremendously exciting to see that LRG1 is a key initiator in diabetic retinopathy.”
Prof. Stephen Moss added, “The good news is that we already have an LRG1-targeting drug ready for clinical trials. This could offer a new, effective option for patients, especially those in the early stages of the disease who don’t respond to existing treatments.”
Dr. Ailish Murray, Director of Grants and Research at Moorfields Eye Charity, highlighted the significance of this discovery, noting that early-stage diabetic retinopathy is often difficult to detect, leading to irreversible damage by the time symptoms appear. “This research could be a vital step forward in preventing the disease and saving the sight of millions of people with diabetes,” she said.
Morag Foreman, Head of Discovery Research at Wellcome, added, “This breakthrough highlights the importance of supporting early-stage research, which can translate into meaningful medical advances. It’s an exciting development with the potential to change lives.”
This discovery opens up new possibilities for the prevention and treatment of diabetic retinopathy, offering hope for millions of people living with diabetes worldwide.
Source: Scitech Daily
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