Understanding how BMP9 protects from diabetes-induced blood retinal barrier breakdown

Breakdown of the blood retinal barrier (BRB) drives progression of diabetic retinopathy. BRB disruption leads to fluid extravasation into the retina, which is known as diabetic macular oedema (DMO). DMO is the most common microvascular complication of diabetes and a leading cause of visual impairment.

Despite clinical improvements with treatments such as anti-VEGFs and laser photocoagulation; there are still 30-40% patients who do not respond to therapy. Therefore, the critical need for new therapeutic alternatives. We propose targeting BMP9 as a new approach to stabilise the retinal vasculature and treat DMO.

BMP9 is a ligand of the TGFβ family with emerging roles in vascular function.

Our preliminary data demonstrate that BMP9 stabilises the vasculature by enhancing barrier properties and inhibiting sprouting capacity. In agreement with this, a recent study reported that BMP9 prevented vascular leakage in STZ-diabetic mice. Consequently, the importance to evaluate if these results in mice translate to humans.

This project will characterise the signalling pathways used by BMP9 to protect the BRB. Importantly, we will use human cells and clinically relevant in vitro diabetes models.

Furthermore, we will test a BMP9- gene therapy, delivered locally to db/db mouse retinas, to protect the retinal vasculature from BRB breakdown.