The quest to prevent sight loss in diabetes 

Diabetes UK has been awarding RD Lawrence Fellowships for many years to researchers who go on to become independent leaders in their field.

In a recent evaluation looking back over 15 years, Dr Jocelyn LeBlanc, Diabetes UK Research Impact Lead, found that 92% of former fellows secured funding to take their research forward within a year of their grant ending and 64% are currently leading their own diabetes research group.

Fellows used words like​‘instrumental’ and​‘life-changing’ to describe their fellowship, and said it helped them get through a career transition point, establish their independence, and mentor the next generation of researchers.

Dr De Rossi is searching for new ways to prevent damage to the blood vessels in the eye and treat early stages of diabetes-related eye disease. 

This is an important and pressing area of research given that diabetes is one of the largest epidemics the world is currently facing. 

Many people with diabetes will gradually develop diabetic retinopathy (DR) and diabetic macular oedema (DMO) due to the high blood sugar levels causing damage to the blood vessels in the light-sensitive part of the eye, called the retina.

These are debilitating complications of diabetes and a leading cause of vision loss in people aged 50 and over. 

If left untreated, vision loss can be a serious long-term effect of diabetes.

Diabetic retinopathy (DR) is a complication that affects the tiny blood vessels (capillaries) at the back of the eye and can result in vision loss.

DR is a slow-progressing disease which starts asymptomatic but can evolve into the sight-threatening advanced stages of diabetic macular oedema (DMO) and/​or proliferative DR.

Diabetic patients need to be tested regularly to detect early signs of DR. With the advancement of imaging techniques, it is now possible to detect diabetic eye disease before patients show any visual symptoms. 

The current standard of care for diabetes-related eye disease relies on drugs that block vascular endothelial growth-factor (VEGF). Unfortunately, these drugs are only effective at the late, vision-threatening stages of the disease.

This means that a patient who is diagnosed with early DR is then closely monitored until their vision deteriorates, as only then these drugs can have a therapeutic effect. 

Only around 50% of patients respond to anti-VEGF treatment.

Even if the anti-VEGF treatment is effective, it is short acting and requires painful monthly eye injections. 

It is possible that once the advanced stage of DR is reached, the damage to the blood vessels cannot be reversed and the treatment stops working.

As cases of DR are increasing there is a dire need to discover new ways to treat this condition.

Dr De Rossi’s research focuses on the role of a molecule called leucine-rich-α2-glycoprotein-1 (LRG1) and its effect on pericytes, a type of cells which tightly wrap around the smaller blood vessels in the retina and provide them with critical support.

In early DR some pericytes start to dysfunction which is thought to trigger a sequence of biological events resulting in vision loss. 

This is recognised as important disease mechanism in early DR but is currently poorly understood. 

Experimental evidence shows that when LRG1 is present, it disrupts pericytes’ function while lack of LRG1 protects from diabetes-induced vascular damage. 

Clinical studies revealed that LRG1 is elevated in the eyes of people with diabetes.

Using preclinical models of diabetes and the early stages of DR, alongside human retinal tissue, Dr De Rossi will investigate the role of LRG1 in early pericyte dysfunction.

She will also test whether blocking LRG1 with an antibody, developed and tested at the Institute of Ophthalmology by Professors Stephen Moss and John Greenwood, could have potential as an earlier treatment for DR to prevent vascular damage and vision loss.

Understanding the subtle but critical changes to retinal blood vessels during the early stages of DR could hold the key to new therapies that would potentially delay or even prevent the irreversible vascular damage in diabetes. 

Dr De Rossi’s work could mark an important step forward in the understanding of the early vascular events in DR. 

The results could provide the evidence needed to support future clinical trials of the therapeutic LRG1 blocking antibody. If successful, this could enable earlier treatment of people with DR, potentially stopping the disease before any vision loss has occurred. 

Dr De Rossi is a vascular biologist who is interested in the processes that drive pathological changes to blood vessels and the development of new therapies to target vascular diseases.