New treatment for diabetic retinopathy

Project background: why was the research important?

Diabetic retinopathy is the leading cause of blindness in the working age population of the UK. It is also among the most frequent complications in diabetic patients. Diabetic retinopathy occurs when blood vessels at the back of the eye leak, become blocked, or grow haphazardly, damaging the retina. The only treatment currently available involves regular, often monthly, injections into the eye. Aside from being unpleasant, this treatment carries an accumulating risk of adverse side effects, and can also become less effective over time. The need to find better treatments is pressing.

What was the aim of the project?

Diabetes has been shown to accelerate ageing in many tissues in the body. When cells in the body age, the process is known as cellular senescence – and an accumulation of senescent cells is known to cause disease. However, comparatively little is known about how diabetes affects tissues in the eye, and the retina in particular.

The aim of this project was to determine whether high levels of glucose, a key characteristic of diabetes, cause the retinal blood vessels to age prematurely, contributing to the problem of leakiness. In particular, the research focused on the effect of glucose on endothelial cells, the building blocks of blood vessels, which deliver oxygen and nutrients to organs. Finally, the project sought to determine whether drugs that target cellular senescence can be used to protect retinal blood vessel cells from accelerated ageing in blood vessels.

What was the outcome?

The research revealed that treating human retinal endothelial cells with high levels of glucose is detrimental to their function. The cells showed lower capacity to form vessel-like structures, and a higher degree of leakiness. Signs of premature cellular ageing were also observed, which suggests that cellular senescence in the retina plays a part in diabetic complications.

Dr Medina’s team then evaluated three different small molecules to test their comparative effectiveness in eliminating senescent cells in human retinas without destroying healthy cells. They identified one, Navitoclax, as being particularly promising. It should be stressed that this discovery, made through studying cells in Petri dishes, is the very first step in a long pathway towards drug development, and a great deal of further testing will be needed in order to confirm Navitoclax’s therapeutic potential.

How will this research help to beat sight loss faster?

The findings of this project have helped to advance understanding of exactly how high levels of glucose damage the eye in diabetic retinopathy. On the strength of these discoveries, the team has secured a grant of over £400,000 from the Biotechnology and Biological Sciences Research Council (BBSRC) to fund a major project that will to allow them to develop their research into the complex biology of ageing in our blood vessels, including the retina. It is hoped that new knowledge acquired from the BBSRC project may facilitate the development of therapies that focus on retinal diseases in future studies.

Dr Medina estimates that the findings from the project funded by Sight Research UK will need to be explored and developed over the course of 1-2 large-scale projects, such as the one funded by BBSRC, in order for the team to gather the data and evidence they need to proceed to a first stage clinical trial.

Further information

You can learn more about the symptoms and current treatments for diabetic retinopathy here and you can find out more about research that we have funded in this area here and here. 

The pursuit of new treatments for people living with sight-threatening disease is made possible by our community of donors – and we cannot thank them enough for their support.