Understanding the Role of EPCR in the Development of Ischaemic Retinopathies

Brief plain language background 

In many diseases of the eye, blood vessels can become damaged and are unable to supply the retina with the high levels of oxygen it requires. The retina is responsible for vision and when blood vessels are lost this can cause serious damage and lead to blindness.
Current treatments cannot address retinal blood vessel damage – just the consequences. Laser photocoagulation, cryotherapy or intraocular surgery are still widely used. Many, but not all patients, respond positively to injections into the eye but these need to be delivered on a recurring basis. We need to find new ways to prevent vision loss
for patients with damaged blood vessels in the retina. One way is to halt further degeneration and repair damaged blood vessels. Based on our recent research, we know that a specific protein, “EPCR”, is very important for repairing blood vessels. Targeting this protein may be a new treatment option.

What problem/knowledge gap does it help address?

Retinal vascular diseases affect patients of all ages. For example, babies born very early often suffer “retinopathy of prematurity” and this can lead to blindness. In adults, small blood vessels in the retina are blocked leading to occlusive disease which patients with diabetes often suffer.

Current treatments are only relevant once vision loss has started and after blood vessels are already damaged. Vessels become leaky and/or undergo abnormal growth which disrupts the structure of the retina. There is a clinical need for new therapies to repair blood vessels at earlier stages. Dr Lechner's approach is to develop therapies which can be given to patients before severe damage occurs to prevent vision loss for people with vascular eye problems.

The team will study cells within blood vessels which have vessel-repairing functions and are identified by “EPCR” to understand more about how EPCR contributes to vessel repair in the retina under damaged conditions.

Aim of the project

The aim of this project is to determine the role that EPCR plays in repairing damaged blood vessels in retina.

Potential impact on people with sight loss

This early-stage discovery research focuses on how certain cells in the retina help repair damaged blood vessels. This knowledge is essential to develop new treatments/interventions. Mapping the timing, signals and behaviours of these cells will identify targets for new treatments to help the eye repair itself before vision loss. Activated protein C (APC) which strongly interacts with EPCR, will be examined as one potential drug target within this programme. Promising approaches will require further validation, safety studies and staged clinical trials but the team are highly motivated to explore a relevant translational pathway whereby this basic research can ultimately benefit patients.