Profiling immune cells during regional ocular inflammation

Why is this research needed?

Uveitis is an umbrella term for immune mediated intraocular inflammation and affects the specialised light sensing cells that comprise the retina. Most cases of non-infectious uveitis are linked to changes in the behaviour of the immune system (the body’s defence against illness and infection), which becomes overactive and mistakenly attacks the eye, leading to retinal damage.

This type of immune-mediated inflammation accounts for a significant prevalence of visual loss in both children and adults. Imaging of uveitis patients reveals a diverse array of disease patterns, some areas of an individual’s retina showing signs of disease but other sites appearing unaffected.

Evidence from other immune-mediated diseases in other organs suggests such inflammation is caused by only a small fraction of infiltrating immune cells. Therefore, we need to gain better understanding as to where these cells are located in the retina, and how they interact with other cells at sites of tissue inflammation.

What is the aim of the project?

This study will generate, for the first time, a comprehensive assessment of molecular disease pathways (endophenotype) that are expressed by specific populations of immune cells found in the retina, and how these influence the distinct disease patterns (pathotype). 

The data will feed major programme funding, which ultimately allows us to move toward understanding at a single-cell level, how cells interact with each other and the tissue. The findings will also inform the optimisation and development of new targets for the next-generation of therapeutics.

How will this research help to beat sight loss faster?

Conventional therapy relies on steroids, but their utility is limited in steroid-refractory patients and is associated with adverse side-effects and shortened life expectancy. In the early 2000s, the University of Bristol research group led the studies of advanced treatment with biologics (e.g. anti-TNFs) which are effective, but at a high economic cost and systemic use requires high doses with the risk of recurrent infections. 

There remains a clinical need to develop precision biologics for local delivery (via intraocular route) with increased effect as they will target and suppress the activity of immune cells within the eye in a more specific and directed way. However, we are still limited by our lack of understanding of the inflammatory process (relative contributions of resident and infiltrating immune cells), and reliable (bio)markers to develop targeted treatments. 

Further information

Further information about uveitis can be found here.