Overview
Posterior uveitis is inflammation in the back of the eye. This can be in the light-sensitive layer of the eye (the retina) or the layer of blood vessels that supplies the retina (the choroid) or both. It involves white blood activity from the immune system that damages the eye and causes sight loss. The same process may also be involved in other conditions such as diabetic retinopathy.
White blood cell activity could be a potential target for treatment, but we don’t know enough about how blood vessels in the retina capture the cells from the general circulation. In this project the research team is looking at what part a meshwork of proteins the surrounds blood vessel walls may play in helping white blood cells enter the retina.
They are using high-resolution 3D imaging to find out where white blood cells prefer to make their entry and are studying the molecules that are active in these regions. The aim is to discover targets that can be blocked with treatment to prevent the immune cells from getting into the retina and causing sight loss.
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Scientific summary
Molecular determinants of regional leukocyte traffic through the retinal vascular plexus.
Intraocular inflammation affecting the posterior segment of the eye, referred to as posterior uveitis, mostly affects individuals of working age and is a significant cause of blindness despite current treatment modalities. The recruitment of leukocytes into the retina is a principle feature of this condition and represents a potentially ideal target for therapy. The contribution of leukocytes to retinal disease, however, is not restricted to autoimmune diseases as recruited immune cells may also contribute to the pathogenesis of conditions such as diabetic retinopathy and retinal ischaemia. Taken together these diseases represent a significant socio-economic burden particularly as current treatments remain inadequate.
Despite substantial advances in our understanding of the factors controlling leukocyte recruitment current experimental approaches have failed to identify and deliver effective therapies. There is therefore a compelling case to gain greater insight into other factors that may control leukocyte recruitment as this will help identify new therapeutic targets.
In this study, therefore, the research team is taking a novel approach and investigating the role played by vascular extracellular components in directing leukocyte traffic to the retina. An avenue of investigation, particularly in the retina, that has been largely ignored. Using recently developed high resolution three dimensional imaging the team is investigating the molecular signature that determines the sites on the retinal vessel wall that are permissive for leukocyte migration. They propose that by investigating the contribution that the vascular extracellular environment makes to permissive regions will reveal novel regulating elements that are tractable to therapeutic intervention.