Researchers led by UCL scientists have discovered a protein that appears to cause diabetic retinopathy, a common eye disease caused when high blood sugar damages blood vessels in the retina. This condition is one of the leading causes of vision loss in working-age adults.
The study, carried out in mice and supported by Diabetes UK, Moorfields Eye Charity and Wellcome, could change the way doctors approach the disease. Future treatments may be able to stop vision loss before it starts, rather than treating damage after it has already occurred.
Protein LRG1 is associated with early retinal damage
The survey results are scientific translational medicinepointed out a protein called LRG1 as an important factor that causes retinal damage in the early stages after the onset of diabetes.
The researchers found that LRG1 causes the cells surrounding the eye’s smallest blood vessels to become overly tense, causing them to become “squeezed.” This narrowing reduces the oxygen supply to the retina, starting a chain reaction that ultimately leads to long-term vision loss.
In experiments using diabetic mouse models, scientists were able to block the activity of LRG1. By doing so, no initial retinal damage occurred and normal eye function was maintained.
Lead author Dr Giulia de Rossi (UCL Institute of Eye Research) said: “Our findings show that diabetic eye disease starts earlier than we thought and that LRG1 is the main cause of this early damage. Targeting this protein could protect vision before serious damage occurs, offering a way to prevent rather than cure blindness for the millions of people living with diabetes.”
Why current treatments are limited
Diabetic retinopathy affects patients with both type 1 and type 2 diabetes. Treatment often begins only after symptoms such as blurred or distorted vision appear. At that point, significant and irreparable damage may have already been done.
Existing treatments focus on another protein called VEGF. However, these treatments are only effective in about half of patients and usually cannot reverse the harm that has already been done.
New research suggests that LRG1 begins to cause eye damage much earlier than VEGF. For this reason, scientists believe this could be a promising new therapeutic target. Therapies designed to block LRG1 may allow early intervention to halt disease progression.
Potential new treatments for diabetic eye disease
Dr Fay Riley, head of research and communications at Diabetes UK, which provided part of the research funding, commented: “Nearly a third of adults with diabetes have some sign of retinopathy, and retinopathy is one of the most feared complications of retinopathy. By identifying the root causes of early damage and offering new treatments, this research holds great promise in helping to protect the sight of the growing number of people with diabetes around the world.”
The UCL research team has already developed drugs that target LRG1. This treatment has been tested in previous studies and additional preclinical studies are currently underway. Scientists say they may move into human clinical trials in the near future.
Researchers believe this treatment may help prevent the development of diabetic retinopathy. Because LRG1 continues to contribute to damage at later stages, it may also benefit people with more advanced disease.
Years of research behind the discovery
The new discovery builds on several years of research by scientists at the UCL Institute of Eye Research, who investigated how LRG1 contributes to eye disease.
Co-authors Professor John Greenwood and Professor Stephen Moss were among the first to identify the role of LRG1 in eye disease. In 2019 they established Senya Therapeutics, a UCL spin-out company set up with support from UCL Business to develop drugs targeting LRG1.
Co-author Professor John Greenwood (UCL Institute of Eye Research), a world expert on LRG1 biology, said: “This study provides important insights into this disease and shows that therapeutic targeting of LRG1 has real clinical potential. The discovery that LRG1 is an early starter that drives diabetic retinopathy is very exciting.”
Co-author Emeritus Professor Stephen Moss (UCL Institute of Eye Research) added: “The good news accompanying these findings is that we have already developed an LRG1 treatment that is ready for clinical trials. This could represent an effective new option for patients, particularly those in the early stages of the disease who are unresponsive to existing treatments.”
Expectations for vision protection for diabetic patients
Dr Irish Murray, director of grants and research at Moorfields Eye Charity, said: “The early stages of diabetic retinopathy are often difficult to detect, and once symptoms appear, many people are left with irreversible damage. This research provides an important and important next step in the prevention of this disease, and an opportunity to save the sight of millions of people living with diabetes now and in the future.”
Morag Foreman, Head of Discovery Research at Wellcome, said: “This is an exciting breakthrough and points to a potential path towards the treatment of diabetic eye disease. These discoveries are the result of cutting-edge discovery research and demonstrate the importance of supporting early science that can lead to meaningful advances in medicine.”
