In brief
Professor Stitt will supervise an investigation of whether a unique version of the protein erythropoietin (EPO) could help to prevent diabetes related eye damage without the potentially harmful side effects normally experienced.
Background to project
The protein erythropoietin (EPO) is produced by the body and helps control the production of red blood cells. EPO has been used widely as a treatment for anaemia, but recent studies suggest it could also help to prevent diabetes-related eye damage. However, if EPO is given to people without anaemia it can over-stimulate the production of red blood cells and increase the risk of a blood clot. Also, giving EPO at the wrong time could actually promote eye damage by stimulating excessive formation of blood vessels.
Professor Alan Stitt’s lab in Belfast have recently developed a unique version of EPO (pHBSP) without the potentially harmful side effects. This protein is currently being used in a clinical trial to protect blood vessels and nerves in people who have experienced a stroke, but its properties mean it could also help to protect against diabetic retinopathy.
Project aims
With support from Diabetes UK, Professor Stitt will supervise a PhD student to investigate the possibility that pHBSP could help to protect against diabetic retinopathy. Specifically, the student will use carefully-planned, sequential experiments incorporating cutting edge molecular cell biology experimental approaches, cell culture systems and animal models of human disease to understand how pHBSP could protect nerves and blood vessels in the retina. These experiments are essential before pHBSP could be considered as a treatment for retinopathy.
Potential benefit to people with diabetes
This research is based in the laboratory but is nevertheless highly relevant to people with diabetic retinopathy, as treatment options for this complication are currently severely limited. Ultimately, this work could lead to important advances and lay the foundation for development of pHBSP to treat the early stages of diabetic retinopathy, which could help prevent devastating vision loss and improve the lives of millions of people with diabetes worldwide.
Summary of progress
Miss Olivia O’Leary was appointed as the PhD student and made an excellent start to her training by obtaining a broad and in-depth perspective on the appropriate literature and by learning the range of technical approaches required. Her first year presentation won the Centre’s prize for first year students.
Preliminary research suggested that pHBSP and EPO have in important role in repairing blood vessels and that pHBSP can help to prevent activation of immune cells in the retina. pHBSP is thought to work by causing adult stem cells found in circulating blood (known as endothelial progenitor cells or EPCs) to home in on damaged areas, where they can bring about repair. Accordingly, the focus of the first year of this studentship has been to examine the chemical signalling pathways that are initiated in these cells by pHBSP. Initial studies yielded variable and inconclusive results, but so far it has found that, when EPCs are exposed to pHBSP in culture, there is an increase in cell-cell communication that promotes cell survival.
The formation of new blood vessels in the body requires endothelial cells (the cells lining blood vessels) to increase in number, migrate to the site where the new vessel is to be formed and create new tube-like structures. EPCs exposed to pHBSP showed an increase in migration but did not show an increased tendency to form tube-like structures in vitro.
EPCs delivered locally to the eye in a mouse model of retinopathy have been shown to integrate into the vascular network of the retina and reduce damage associated with the condition. The research has begun to determine the ability of pHBSP to improve the longevity of EPCs but work examining its effect on their proliferation and to determine if improved repair of the vascular network is observed is now ongoing.